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Sample records for antibody-dependent enhancement dengue

  1. Antibody-dependent enhancement of dengue virus infection is inhibited by SA-17, a doxorubicin derivative

    NARCIS (Netherlands)

    Ayala Nunez, Vanesa; Jarupathirun, Patsaporn; Kaptein, Suzanne; Neyts, Johan; Smit, Jolanda

    2013-01-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus (DENV)-induced disease during a heterologous re-infection. Despite ADE's clinical impact, only a few antiviral compounds have been assessed for their anti-ADE activity. We reported earlier tha

  2. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    Science.gov (United States)

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong

    2011-07-26

    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  3. Antibody-dependent enhancement of dengue virus infection is inhibited by SA-17, a doxorubicin derivative.

    Science.gov (United States)

    Ayala-Nuñez, Nilda V; Jarupathirun, Patsaporn; Kaptein, Suzanne J F; Neyts, Johan; Smit, Jolanda M

    2013-10-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus (DENV)-induced disease during a heterologous re-infection. Despite ADE's clinical impact, only a few antiviral compounds have been assessed for their anti-ADE activity. We reported earlier that SA-17, a doxorubicin derivative, efficiently inhibits the in vitro infection of DENV and yellow fever virus. Here we explored SA-17's mechanism of inhibition and investigated if the compound is active against ADE of DENV infection. Since enhanced infectivity stimulated by antibodies has been observed with standard and immature DENV, both types of virions were included in the study. We observed that SA-17 (i) inhibits DENV infection by preventing binding/entry to the cell and (ii) interferes with antibody-mediated infection of both standard and immature DENV2. SA-17 markedly reduced the infectivity of DENV2 in ADE conditions, with IC50s ranging from 0.26 to 2.89μM. The compound exerted its activity when added before, during, and after antibody-opsonization of standard and immature virus. Thus, molecules with the characteristics of SA-17 may be attractive antiviral agents since they can be used both to block DENV2 entry during primary and secondary infection and to inhibit ADE of standard and immature virus. PMID:23994499

  4. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus.

    Science.gov (United States)

    Dejnirattisai, Wanwisa; Supasa, Piyada; Wongwiwat, Wiyada; Rouvinski, Alexander; Barba-Spaeth, Giovanna; Duangchinda, Thaneeya; Sakuntabhai, Anavaj; Cao-Lormeau, Van-Mai; Malasit, Prida; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2016-09-01

    Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern, with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue virus (DENV), a flavivirus closely related to ZIKV. Here we investigated the serological cross-reaction between the two viruses. Plasma immune to DENV showed substantial cross-reaction to ZIKV and was able to drive antibody-dependent enhancement (ADE) of ZIKV infection. Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV. PMID:27339099

  5. Antibody-Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses.

    Science.gov (United States)

    Flipse, Jacky; Diosa-Toro, Mayra A; Hoornweg, Tabitha E; van de Pol, Denise P I; Urcuqui-Inchima, Silvio; Smit, Jolanda M

    2016-01-01

    The dogma is that the human immune system protects us against pathogens. Yet, several viruses, like dengue virus, antagonize the hosts' antibodies to enhance their viral load and disease severity; a phenomenon called antibody-dependent enhancement of infection. This study offers novel insights in the molecular mechanism of antibody-mediated enhancement (ADE) of dengue virus infection in primary human macrophages. No differences were observed in the number of bound and internalized DENV particles following infection in the absence and presence of enhancing concentrations of antibodies. Yet, we did find an increase in membrane fusion activity during ADE of DENV infection. The higher fusion activity is coupled to a low antiviral response early in infection and subsequently a higher infection efficiency. Apparently, subtle enhancements early in the viral life cycle cascades into strong effects on infection, virus production and immune response. Importantly, and in contrast to other studies, the antibody-opsonized virus particles do not trigger immune suppression and remain sensitive to interferon. Additionally, this study gives insight in how human macrophages interact and respond to viral infections and the tight regulation thereof under various conditions of infection. PMID:27380892

  6. Antibody-Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses

    Science.gov (United States)

    Flipse, Jacky; Diosa-Toro, Mayra A.; Hoornweg, Tabitha E.; van de Pol, Denise P. I.; Urcuqui-Inchima, Silvio; Smit, Jolanda M.

    2016-01-01

    The dogma is that the human immune system protects us against pathogens. Yet, several viruses, like dengue virus, antagonize the hosts’ antibodies to enhance their viral load and disease severity; a phenomenon called antibody-dependent enhancement of infection. This study offers novel insights in the molecular mechanism of antibody-mediated enhancement (ADE) of dengue virus infection in primary human macrophages. No differences were observed in the number of bound and internalized DENV particles following infection in the absence and presence of enhancing concentrations of antibodies. Yet, we did find an increase in membrane fusion activity during ADE of DENV infection. The higher fusion activity is coupled to a low antiviral response early in infection and subsequently a higher infection efficiency. Apparently, subtle enhancements early in the viral life cycle cascades into strong effects on infection, virus production and immune response. Importantly, and in contrast to other studies, the antibody-opsonized virus particles do not trigger immune suppression and remain sensitive to interferon. Additionally, this study gives insight in how human macrophages interact and respond to viral infections and the tight regulation thereof under various conditions of infection. PMID:27380892

  7. Molecular mechanisms involved in antibody-dependent enhancement of dengue virus infection in humans

    NARCIS (Netherlands)

    Flipse, Jacky; Wilschut, Jan; Smit, Jolanda M.

    2013-01-01

    Dengue is the most common arthropod-borne viral infection in humans with similar to 50 million cases annually worldwide. In recent decades, a steady increase in the number of severe dengue cases has been seen. Severe dengue disease is most often observed in individuals that have pre-existing immunit

  8. Manipulation of immunodominant dengue virus E protein epitopes reduces potential antibody-dependent enhancement

    Directory of Open Access Journals (Sweden)

    Hughes Holly R

    2012-06-01

    Full Text Available Abstract Background Dengue viruses (DENV are the most important arboviruses of humans and cause significant disease. Infection with DENV elicits antibody responses to the envelope glycoprotein, predominantly against immunodominant, cross-reactive, weakly-neutralizing epitopes. These weakly-neutralizing antibodies are implicated in enhancing infection via Fcγ receptor bearing cells and can lead to increased viral loads that are associated with severe disease. Here we describe results from the development and testing of cross-reactivity reduced DENV-2 DNA vaccine candidates that contain substitutions in immunodominant B cell epitopes of the fusion peptide and domain III of the envelope protein. Results Cross-reactivity reduced and wild-type vaccine candidates were similarly immunogenic in outbred mice and elicited high levels of neutralizing antibody, however mice immunized with cross-reactivity reduced vaccines produced significantly reduced levels of immunodominant cross-reactive antibodies. Sera from mice immunized with wild-type, fusion peptide-, or domain III- substitution containing vaccines enhanced heterologous DENV infection in vitro, unlike sera from mice immunized with a vaccine containing a combination of both fusion peptide and domain III substitutions. Passive transfer of immune sera from mice immunized with fusion peptide and domain III substitutions also reduced the development of severe DENV disease in AG129 mice when compared to mice receiving wild type immune sera. Conclusions Reducing cross-reactivity in the envelope glycoprotein of DENV may be an approach to improve the quality of the anti-DENV immune response.

  9. Molecular mechanisms of dengue virus infection : cell tropism, antibody-dependent enhancement, and cytokines

    NARCIS (Netherlands)

    Flipse, Jacobus

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease in humans. Although most infections occur in the (sub)tropical areas, recent outbreaks in Italy and Madeira indicate that the virus is spreading into Europe. Despite its relevance, no vaccine or medications are available against this virus. T

  10. Mosquito Saliva Increases Endothelial Permeability in the Skin, Immune Cell Migration, and Dengue Pathogenesis during Antibody-Dependent Enhancement.

    Science.gov (United States)

    Schmid, Michael A; Glasner, Dustin R; Shah, Sanjana; Michlmayr, Daniela; Kramer, Laura D; Harris, Eva

    2016-06-01

    Dengue remains the most prevalent arthropod-borne viral disease in humans. While probing for blood vessels, Aedes aegypti and Ae. albopictus mosquitoes transmit the four serotypes of dengue virus (DENV1-4) by injecting virus-containing saliva into the skin. Even though arthropod saliva is known to facilitate transmission and modulate host responses to other pathogens, the full impact of mosquito saliva on dengue pathogenesis is still not well understood. Inoculating mice lacking the interferon-α/β receptor intradermally with DENV revealed that mosquito salivary gland extract (SGE) exacerbates dengue pathogenesis specifically in the presence of enhancing serotype-cross-reactive antibodies-when individuals already carry an increased risk for severe disease. We further establish that SGE increases viral titers in the skin, boosts antibody-enhanced DENV infection of dendritic cells and macrophages in the dermis, and amplifies dendritic cell migration to skin-draining lymph nodes. We demonstrate that SGE directly disrupts endothelial barrier function in vitro and induces endothelial permeability in vivo in the skin. Finally, we show that surgically removing the site of DENV transmission in the skin after 4 hours rescued mice from disease in the absence of SGE, but no longer prevented lethal antibody-enhanced disease when SGE was present. These results indicate that SGE accelerates the dynamics of dengue pathogenesis after virus transmission in the skin and induces severe antibody-enhanced disease systemically. Our study reveals novel aspects of dengue pathogenesis and suggests that animal models of dengue and pre-clinical testing of dengue vaccines should consider mosquito-derived factors as well as enhancing antibodies. PMID:27310141

  11. Mosquito Saliva Increases Endothelial Permeability in the Skin, Immune Cell Migration, and Dengue Pathogenesis during Antibody-Dependent Enhancement

    Science.gov (United States)

    Schmid, Michael A.; Glasner, Dustin R.; Shah, Sanjana; Michlmayr, Daniela; Kramer, Laura D.; Harris, Eva

    2016-01-01

    Dengue remains the most prevalent arthropod-borne viral disease in humans. While probing for blood vessels, Aedes aegypti and Ae. albopictus mosquitoes transmit the four serotypes of dengue virus (DENV1-4) by injecting virus-containing saliva into the skin. Even though arthropod saliva is known to facilitate transmission and modulate host responses to other pathogens, the full impact of mosquito saliva on dengue pathogenesis is still not well understood. Inoculating mice lacking the interferon-α/β receptor intradermally with DENV revealed that mosquito salivary gland extract (SGE) exacerbates dengue pathogenesis specifically in the presence of enhancing serotype-cross-reactive antibodies—when individuals already carry an increased risk for severe disease. We further establish that SGE increases viral titers in the skin, boosts antibody-enhanced DENV infection of dendritic cells and macrophages in the dermis, and amplifies dendritic cell migration to skin-draining lymph nodes. We demonstrate that SGE directly disrupts endothelial barrier function in vitro and induces endothelial permeability in vivo in the skin. Finally, we show that surgically removing the site of DENV transmission in the skin after 4 hours rescued mice from disease in the absence of SGE, but no longer prevented lethal antibody-enhanced disease when SGE was present. These results indicate that SGE accelerates the dynamics of dengue pathogenesis after virus transmission in the skin and induces severe antibody-enhanced disease systemically. Our study reveals novel aspects of dengue pathogenesis and suggests that animal models of dengue and pre-clinical testing of dengue vaccines should consider mosquito-derived factors as well as enhancing antibodies. PMID:27310141

  12. CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice.

    Science.gov (United States)

    Zellweger, Raphaël M; Eddy, William E; Tang, William W; Miller, Robyn; Shresta, Sujan

    2014-10-15

    Dengue virus (DENV) causes pathologies ranging from the febrile illness dengue fever to the potentially lethal severe dengue disease. A major risk factor for developing severe dengue disease is the presence of subprotective DENV-reactive Abs from a previous infection (or from an immune mother), which can induce Ab-dependent enhancement of infection (ADE). However, infection in the presence of subprotective anti-DENV Abs does not always result in severe disease, suggesting that other factors influence disease severity. In this study we investigated how CD8(+) T cell responses influence the outcome of Ab-mediated severe dengue disease. Mice were primed with aluminum hydroxide-adjuvanted UV-inactivated DENV prior to challenge with DENV. Priming failed to induce robust CD8(+) T cell responses, and it induced nonneutralizing Ab responses that increased disease severity upon infection. Transfer of exogenous DENV-activated CD8(+) T cells into primed mice prior to infection prevented Ab-dependent enhancement and dramatically reduced viral load. Our results suggest that in the presence of subprotective anti-DENV Abs, efficient CD8(+) T cell responses reduce the risk of Ab-mediated severe dengue disease. PMID:25217165

  13. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    International Nuclear Information System (INIS)

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection

  14. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    Energy Technology Data Exchange (ETDEWEB)

    Chotiwan, Nunya; Roehrig, John T. [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Schlesinger, Jacob J. [Department of Medicine, University of Rochester, Rochester, NY 14642 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H., E-mail: yxh0@cdc.gov [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2014-05-15

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.

  15. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

    Directory of Open Access Journals (Sweden)

    Koji Ichiyama

    Full Text Available Curdlan sulfate (CRDS, a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV. CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion. The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  16. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection.

    Science.gov (United States)

    Choy, Milly M; Zhang, Summer L; Costa, Vivian V; Tan, Hwee Cheng; Horrevorts, Sophie; Ooi, Eng Eong

    2015-11-01

    The mosquito-borne dengue virus (DENV) is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP) to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue. PMID:26565697

  17. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection.

    Directory of Open Access Journals (Sweden)

    Milly M Choy

    2015-11-01

    Full Text Available The mosquito-borne dengue virus (DENV is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue.

  18. Advances in antibody-dependent enhancement for dengue virus%登革病毒抗体依赖性感染增强作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    宋克玉; 李晓峰; 江振友; 秦成峰

    2012-01-01

    Antibody-dependent enhancement ( ADE ) present in the infection of dengue virus ( DENV ) has huge effect on the effect of treatment. ADE of virus replication is believed to occur when heterotypic, nonneutralizing antibody present in the host from a previous DENV infection binds to the virus via binding to the Fey receptors ( Fc-yR ) during a subsequent heterotypic infection but is unable to neutralize the virus. The overall result is an increase in virus replication and the level of viremia, which is associated with an increase in disease severity. Studies on the immune response of ADE can contribute to the derelopment of effective vaccines and drugs. In this review, the resent advances of ADE in dengue virus are discussed.%抗体依赖性感染增强作用(antibody-dependent enhancement,ADE)在登革病毒的致病机制中发挥重要作用.在存在亚中和浓度抗体的条件下,登革病毒可通过Fc受体或补体受体等途径进入靶细胞,进而导致ADE的发生.ADE的发生受病毒和宿主一系列复杂因素的调节,直接影响患者的临床表现和病情进展,对其作用机制的研究有助于加深对登革出血热发病机制的认识,对登革热疫苗以及治疗性抗体的研发具有重要意义.本文综述了登革病毒ADE的研究进展.

  19. Dynamic effects of antibody-dependent enhancement on the fitness of viruses

    OpenAIRE

    Cummings, Derek A. T.; Schwartz, Ira B.; Billings, Lora; Shaw, Leah B.; Burke, Donald S

    2005-01-01

    Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which ADE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. ...

  20. Antibody dependent enhancement of frog virus 3 infection

    Directory of Open Access Journals (Sweden)

    Penny Emily

    2010-02-01

    Full Text Available Abstract Background Viruses included in the family Iridoviridae are large, icosahedral, dsDNA viruses that are subdivided into 5 genera. Frog virus 3 (FV3 is the type species of the genus Ranavirus and the best studied iridovirus at the molecular level. Typically, antibodies directed against a virus act to neutralize the virus and limit infection. Antibody dependent enhancement occurs when viral antibodies enhance infectivity of the virus rather than neutralize it. Results Here we show that anti-FV3 serum present at the time of FV3 infection enhances infectivity of the virus in two non-immune teleost cell lines. We found that antibody dependent enhancement of FV3 was dependent on the Fc portion of anti-FV3 antibodies but not related to complement. Furthermore, the presence of anti-FV3 serum during an FV3 infection in a non-immune mammalian cell line resulted in neutralization of the virus. Our results suggest that a cell surface receptor specific to teleost cell lines is responsible for the enhancement. Conclusions This report represents the first evidence of antibody dependent enhancement in iridoviruses. The data suggests that anti-FV3 serum can either neutralize or enhance viral infection and that enhancement is related to a novel antibody dependent enhancement pathway found in teleosts that is Fc dependent.

  1. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    OpenAIRE

    Pei Xuan Lee; Li Ching Ong; Eshele Anak Libau; Sylvie Alonso

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upo...

  2. Enhancement of antibody-dependent mechanisms of tumor cell lysis by a targeted activator of complement.

    Science.gov (United States)

    Imai, Masaki; Ohta, Rieko; Varela, Juan C; Song, Hongbin; Tomlinson, Stephen

    2007-10-01

    Complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies (mAb). We investigated a novel strategy to overwhelm complement inhibitor activity and amplify complement activation on tumor cells. The C3-binding domain of human complement receptor 2 (CR2; CD21) was linked to the complement-activating Fc region of human IgG1 (CR2-Fc), and the ability of the construct to target and amplify complement deposition on tumor cells was investigated. CR2 binds C3 activation fragments, and CR2-Fc targeted tumor cells by binding to C3 initially deposited by a tumor-specific antibody. Complement deposition on Du145 cells (human prostate cancer cell line) and anti-MUC1 mAb-mediated complement-dependent lysis of Du145 cells were significantly enhanced by CR2-Fc. Anti-MUC1 antibody-dependent cell-mediated cytotoxicity of Du145 by human peripheral blood mononuclear cells was also significantly enhanced by CR2-Fc in both the presence and the absence of complement. Radiolabeled CR2-Fc targeted to s.c. Du145 tumors in nude mice treated with anti-MUC1 mAb, validating the targeting strategy in vivo. A metastatic model was used to investigate the effect of CR2-Fc in a therapeutic paradigm. Administration of CR2-Fc together with mAb therapy significantly improved long-term survival of nude mice challenged with an i.v. injection of EL4 cells. The data show that CR2-Fc enhances the therapeutic efficacy of antibody therapy, and the construct may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density. PMID:17909064

  3. Enhancement of antibody-dependent mechanisms of tumor cell lysis by a targeted activator of complement.

    Science.gov (United States)

    Imai, Masaki; Ohta, Rieko; Varela, Juan C; Song, Hongbin; Tomlinson, Stephen

    2007-10-01

    Complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies (mAb). We investigated a novel strategy to overwhelm complement inhibitor activity and amplify complement activation on tumor cells. The C3-binding domain of human complement receptor 2 (CR2; CD21) was linked to the complement-activating Fc region of human IgG1 (CR2-Fc), and the ability of the construct to target and amplify complement deposition on tumor cells was investigated. CR2 binds C3 activation fragments, and CR2-Fc targeted tumor cells by binding to C3 initially deposited by a tumor-specific antibody. Complement deposition on Du145 cells (human prostate cancer cell line) and anti-MUC1 mAb-mediated complement-dependent lysis of Du145 cells were significantly enhanced by CR2-Fc. Anti-MUC1 antibody-dependent cell-mediated cytotoxicity of Du145 by human peripheral blood mononuclear cells was also significantly enhanced by CR2-Fc in both the presence and the absence of complement. Radiolabeled CR2-Fc targeted to s.c. Du145 tumors in nude mice treated with anti-MUC1 mAb, validating the targeting strategy in vivo. A metastatic model was used to investigate the effect of CR2-Fc in a therapeutic paradigm. Administration of CR2-Fc together with mAb therapy significantly improved long-term survival of nude mice challenged with an i.v. injection of EL4 cells. The data show that CR2-Fc enhances the therapeutic efficacy of antibody therapy, and the construct may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.

  4. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-06-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  5. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Pei Xuan Lee

    2016-06-01

    Full Text Available Dengue virus (DENV causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers.

  6. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice

    Science.gov (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie

    2016-01-01

    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  7. Enhanced antibody-dependent cellular phagocytosis by chimeric monoclonal antibodies with tandemly repeated Fc domains.

    Science.gov (United States)

    Nagashima, Hiroaki; Ootsubo, Michiko; Fukazawa, Mizuki; Motoi, Sotaro; Konakahara, Shu; Masuho, Yasuhiko

    2011-04-01

    We previously reported that chimeric monoclonal antibodies (mAbs) with tandemly repeated Fc domains, which were developed by introducing tandem repeats of Fc domains downstream of 2 Fab domains, augmented binding avidities for all Fcγ receptors, resulting in enhanced antibody (Ab)-dependent cellular cytotoxicity. Here we investigated regarding Ab-dependent cellular phagocytosis (ADCP) mediated by these chimeric mAbs, which is considered one of the most important mechanisms that kills tumor cells, using two-color flow cytometric methods. ADCP mediated by T3-Ab, a chimeric mAb with 3 tandemly repeated Fc domains, was 5 times more potent than that by native anti-CD20 M-Ab (M-Ab hereafter). Furthermore, T3-Ab-mediated ADCP was resistant to competitive inhibition by intravenous Ig (IVIG), although M-Ab-mediated ADCP decreased in the presence of IVIG. An Fcγ receptor-blocking study demonstrated that T3-Ab mediated ADCP via both FcγRIA and FcγRIIA, whereas M-Ab mediated ADCP exclusively via FcγRIA. These results suggest that chimeric mAbs with tandemly repeated Fc domains enhance ADCP as well as ADCC, and that Fc multimerization may significantly enhance the efficacy of therapeutic Abs. PMID:21215693

  8. Immunological enhancement and the pathogenesis of dengue haemorrhagic fever.

    OpenAIRE

    Porterfield, J S

    1982-01-01

    Laboratory studies have provided evidence that the replication of dengue viruses in preparations of primary peripheral blood mononuclear cells of human or simian origin, or in macrophage-like cell lines of human or murine origin, may be enhanced by sub-neutralizing concentrations of homotypic dengue antibody, by heterotypic dengue antibody, or by antibody against heterologous flaviviruses. The mechanism underlying this phenomenon is discussed in the context of dengue haemorrhagic fever and th...

  9. The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages.

    Science.gov (United States)

    Hohdatsu, T; Tokunaga, J; Koyama, H

    1994-01-01

    Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc gamma R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc gamma R on feline macrophage.

  10. Recent progress in dengue vaccine development

    Institute of Scientific and Technical Information of China (English)

    Jianchun; Wei; Hui; Chen; Jing; An

    2014-01-01

    Dengue virus(DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations.

  11. Recent progress in dengue vaccine development.

    Science.gov (United States)

    Wei, Jianchun; Chen, Hui; An, Jing

    2014-12-01

    Dengue virus (DENV) has four distinct serotypes. DENV infection can result in classic dengue fever and life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent decades, DENV infection has become an important public health concern in epidemic-prone areas. Vaccination is the most effective measure to prevent and control viral infections. However, several challenges impede the development of effective DENV vaccines, such as the lack of suitable animal models and the antibody-dependent enhancement phenomenon. Although no licensed DENV vaccine is available, significant progress has been made. This review summarizes candidate DENV vaccines from recent investigations. PMID:25547681

  12. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release.

    Science.gov (United States)

    Robinson, W E; Montefiori, D C; Gillespie, D H; Mitchell, W M

    1989-01-01

    Antibody-dependent enhancement (ADE) of human immunodeficiency virus type 1 (HIV-1) infection in vitro has been described recently and was shown to occur by two mechanisms: either participation of the alternative pathway of complement or to involve an Fc receptor-mediated, complement-independent mechanism. Complement-mediated ADE results in an accelerated cytopathic effect in target cells that can abrogate the protective properties of neutralizing antibodies. This study characterizes the surface antigens of MT-2 cells using flow cytometric analysis and shows that these cells express high levels of both CD4 and complement receptor type 2 (CR2) while several CD4+ cell lines that do not demonstrate complement-mediated ADE lack high levels of complement receptors. Further, utilizing MT-2 cell cultures, it is demonstrated that complement-mediated ADE of HIV-1 infection is conferred by the sera from more than 80% of HIV-1 antibody-positive individuals (N = 85). Complement-mediated ADE of HIV-1 infection causes an acceleration of several parameters indicative of HIV-1 infection in vitro including increased HIV-1 antigen synthesis as detected by indirect immunofluorescence, RNA accumulation as measured by a solution hybridization protocol, reverse transcriptase release, and progeny virus production. PMID:2465404

  13. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2

    NARCIS (Netherlands)

    Voorham, Julia M. da Silva; Rodenhuis-Zybert, Izabela A.; Nunez, Nilda Vanesa Ayala; Colpitts, Tonya M.; van der Ende-Metselaar, Heidi; Fikrig, Erol; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.

    2012-01-01

    Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM

  14. Dengue virus cell entry : Unraveling the role of antibodies, maturation status, and antiviral drugs

    NARCIS (Netherlands)

    Ayala Nunez, Vanesa

    2014-01-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus-induced disease during a heterologous re-infection. Pre-existing cross-reactive anti-dengue antibodies are generally believed to bind to the newly infecting DENV and target the antibody-virus

  15. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab.

    Science.gov (United States)

    Fujii, Rika; Friedman, Eitan R; Richards, Jacob; Tsang, Kwong Y; Heery, Christopher R; Schlom, Jeffrey; Hodge, James W

    2016-06-01

    Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab. PD-L1 expression was markedly upregulated by IFN-γ in all 4 chordoma cell lines, which significantly increased sensitivity to ADCC. Brachyury is a transcription factor that is uniformly expressed in chordoma. Clinical trials are ongoing in which chordoma patients are treated with brachyury-specific vaccines. Co-incubating chordoma cells with brachyury-specific CD8+ T cells resulted in significant upregulation of PD-L1 on the tumor cells, mediated by the CD8+ T cells' IFN-γ production, and increased sensitivity of chordoma cells to avelumab-mediated ADCC. Residential cancer stem cell subpopulations of chordoma cells were also killed by avelumab-mediated ADCC to the same degree as non-cancer stem cell populations. These findings suggest that as a monotherapy for chordoma, avelumab may enable endogenous NK cells, while in combination with T-cell immunotherapy, such as a vaccine, avelumab may enhance NK-cell killing of chordoma cells via ADCC.

  16. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.

    Science.gov (United States)

    Cooley, S; Burns, L J; Repka, T; Miller, J S

    1999-10-01

    Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells. PMID:10517495

  17. Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Bruckheimer

    2009-06-01

    Full Text Available EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID mice (which have functional NK cells and monocytes and SCID nonobese diabetic (NOD mice (which largely lack functional NK cells and monocytes. Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells.

  18. Dengue

    Science.gov (United States)

    ... take... Epidemiology Transmission, information on epidemics and stats... Entomology & Ecology Mosquito that spreads dengue and its ecology... ... Prevention If You Think You Have Dengue Epidemiology Entomology/Ecology Mosquito Life-Cycle Mosquito Aquatic Habitats Dengue ...

  19. Enhancing knowledge and awareness of dengue during a prospective study of dengue fever.

    Science.gov (United States)

    Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna; Widjaja, Susana; Listianingsih, Erlin; Ma'roef, Chairin; Wuryadi, Suharyono; Alisjahbana, Bachti; Rudiman, Irani; McArdle, James L; Porter, Kevin R

    2004-09-01

    In 1992, the Indonesian CDC implemented strategies to control and prevent dengue fever (DF) by including community involvement to reduce larva breeding sites and a mass health education program. To contribute to this effort, we incorporated an educational component into a prospective study of DF conducted at two textile factories in Bandung. This education provided: a lecture on the signs and symptoms of dengue and ways to prevent the disease, posters in the health clinic at each factory and handouts given to each volunteer with an explanation of symptoms. Upon enrollment, each participant completed a questionnaire to gather demographic information. Additionally they were given a brief (non-standardized) test (PRE-test) of their dengue knowledge, which was verbally administered by the study physicians. Five questions (15 point system) were designed to assess the participant's ability to recognize and describe aspects of dengue in lay terms. The subject material included: the symptoms of acute DF, transmission of dengue virus, and basic steps for disease prevention. The same questionnaire was re-administered 18 months later (POST-test), and the results were compared. A total of 2,340 participants completed both the PRE- and POST-tests; there were 1,373 males and 967 females, median age 36 years (range 18-59). Only 0.3% of participants scored EXCELLENT (15-14 points) on the PRE-test whereas 8.4% scored EXCELLENT on the POST-test. Fewer participants scored VERY BAD (2-0 points) on the POST-test compared to the PRE-test (1.4% vs 4.0%). The average raw scores for the PRE- and POST-tests were 7.8 and 10.1, respectively. Improvement of individual scores correlated highly with educational level. No significant correlation was identified for gender, age, factory location or a diagnosis of dengue during the study. These findings demonstrate that our prospective study enhanced knowledge and awareness of dengue in the volunteers.

  20. Generation of Monoclonal Antibodies against Dengue Virus Type 4 and Identification of Enhancing Epitopes on Envelope Protein.

    Directory of Open Access Journals (Sweden)

    Chung-Tao Tang

    Full Text Available The four serotypes of dengue virus (DENV1-4 pose a serious threat to global health. Cross-reactive and non-neutralizing antibodies enhance viral infection, thereby exacerbating the disease via antibody-dependent enhancement (ADE. Studying the epitopes targeted by these enhancing antibodies would improve the immune responses against DENV infection. In order to investigate the roles of antibodies in the pathogenesis of dengue, we generated a panel of 16 new monoclonal antibodies (mAbs against DENV4. Using plaque reduction neutralization test (PRNT, we examined the neutralizing activity of these mAbs. Furthermore, we used the in vitro and in vivo ADE assay to evaluate the enhancement of DENV infection by mAbs. The results indicate that the cross-reactive and poorly neutralizing mAbs, DD11-4 and DD18-5, strongly enhance DENV1-4 infection of K562 cells and increase mortality in AG129 mice. The epitope residues of these enhancing mAbs were identified using virus-like particle (VLP mutants. W212 and E26 are the epitope residues of DD11-4 and DD18-5, respectively. In conclusion, we generated and characterized 16 new mAbs against DENV4. DD11-4 and D18-5 possessed non-neutralizing activities and enhanced viral infection. Moreover, we identified the epitope residues of enhancing mAbs on envelope protein. These results may provide useful information for development of safe dengue vaccine.

  1. Augmentation of natural killer cell and antibody-dependent cellular cytotoxicity in BALB/c mice by sulforaphane, a naturally occurring isothiocyanate from broccoli through enhanced production of cytokines IL-2 and IFN-gamma.

    Science.gov (United States)

    Thejass, P; Kuttan, G

    2006-01-01

    Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-gamma in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide. PMID:16997793

  2. Dengue

    Science.gov (United States)

    Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It ... the world. Outbreaks occur in the rainy season. Dengue is rare in the United States. Symptoms include ...

  3. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  4. Enhancing knowledge and awareness of dengue during a prospective study of dengue fever.

    Science.gov (United States)

    Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna; Widjaja, Susana; Listianingsih, Erlin; Ma'roef, Chairin; Wuryadi, Suharyono; Alisjahbana, Bachti; Rudiman, Irani; McArdle, James L; Porter, Kevin R

    2004-09-01

    In 1992, the Indonesian CDC implemented strategies to control and prevent dengue fever (DF) by including community involvement to reduce larva breeding sites and a mass health education program. To contribute to this effort, we incorporated an educational component into a prospective study of DF conducted at two textile factories in Bandung. This education provided: a lecture on the signs and symptoms of dengue and ways to prevent the disease, posters in the health clinic at each factory and handouts given to each volunteer with an explanation of symptoms. Upon enrollment, each participant completed a questionnaire to gather demographic information. Additionally they were given a brief (non-standardized) test (PRE-test) of their dengue knowledge, which was verbally administered by the study physicians. Five questions (15 point system) were designed to assess the participant's ability to recognize and describe aspects of dengue in lay terms. The subject material included: the symptoms of acute DF, transmission of dengue virus, and basic steps for disease prevention. The same questionnaire was re-administered 18 months later (POST-test), and the results were compared. A total of 2,340 participants completed both the PRE- and POST-tests; there were 1,373 males and 967 females, median age 36 years (range 18-59). Only 0.3% of participants scored EXCELLENT (15-14 points) on the PRE-test whereas 8.4% scored EXCELLENT on the POST-test. Fewer participants scored VERY BAD (2-0 points) on the POST-test compared to the PRE-test (1.4% vs 4.0%). The average raw scores for the PRE- and POST-tests were 7.8 and 10.1, respectively. Improvement of individual scores correlated highly with educational level. No significant correlation was identified for gender, age, factory location or a diagnosis of dengue during the study. These findings demonstrate that our prospective study enhanced knowledge and awareness of dengue in the volunteers. PMID:15689076

  5. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2010-12-01

    Full Text Available Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmitted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theories or hypotheses immuno-patogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus infection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide a decent home and healthy, drinking water supply and proper waste disposal.

  6. Enhanced performance of an innovative dengue IgG/IgM rapid diagnostic test using an anti-dengue EDI monoclonal antibody and dengue virus antigen

    OpenAIRE

    Jihoo Lee; Young-Eun Kim; Hak-Yong Kim; Mangalam Sinniah; Chom-Kyu Chong; Hyun-Ok Song

    2015-01-01

    High levels of anti-dengue IgM or IgG can be detected using numerous rapid diagnostic tests (RDTs). However, the sensitivity and specificity of these tests are reduced by changes in envelope glycoprotein antigenicity that inevitably occur in limited expression systems. A novel RDT was designed to enhance diagnostic sensitivity. Dengue viruses cultured in animal cells were used as antigens to retain the native viral coat protein. Monoclonal antibodies (mAbs) were then developed, for the first ...

  7. Induction of IFNα or IL-12 depends on differentiation of THP-1 cells in dengue infections without and with antibody enhancement

    Directory of Open Access Journals (Sweden)

    Chen Rong-Fu

    2012-12-01

    Full Text Available Abstract Background Appropriate induction of the early Th1 cytokine IL-12 is a critical defense directed against viral infection. We have previously shown that different viruses elicited either IL-12 or IFNα dependent Th1 reactions. Using dengue-2 virus, we sought to explore how dengue-2 induced IL-12 or IFNα expression by monocytic and its derived dendritic cells. Methods We employed human monocytic cell line, THP-1, to investigate whether differentiation of monocytic cells is involved in the switch between IFNα and IL-12 induction. Flow cytometry, RT-PCR and ELISA were respectively used to determine cell differentiation, IL-12 and IFNα mRNA expression and protein production. Results THP-1, expressing CD123, which is a plasmacytoid dendritic cell marker, but not CD14, CD11b or CD11c revealed IFNα mRNA expression while stimulated by dengue-2. In contrast, PMA-induced THP-1 differentiation toward monocytic cells expressed CD11b+, and CD14+, but not CD123, and revealed exclusively IL-12 expression while stimulated by dengue-2. Further studies showed that CD123+ expressing THP-1 cells elicited higher IFNα expression in dose and time dependent induction after infection, and PMA-induced monocytic differentiation of THP-1 cells revealed IL-12 expression. Antibody-dependent enhancement of DEN-2 infection significantly suppressed the DEN-2 induced IL-12 p40 expression in monocytic differentiated THP-1 cells. Conclusions Clarification and modulation of the early Th1 reaction in different monocytic cells may change or prevent complication from dengue infection.

  8. Autophagic machinery activated by dengue virus enhances virus replication

    International Nuclear Information System (INIS)

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication

  9. The Potential Impact of Vaccination on the Dynamics of Dengue Infections.

    Science.gov (United States)

    Knipl, Diána; Moghadas, Seyed M

    2015-12-01

    Dengue, classified as a 'neglected topical disease', is currently regarded globally as the most important mosquito-borne viral disease, which inflicts substantial socioeconomic and health burden in many tropical and subtropical regions of the world. While efforts continue towards developing and improving the efficacy of a tetravalent vaccine to protect individuals against all dengue virus serotypes, the long-term epidemiological impact of vaccination remains elusive. We develop a serotype-specific, vector-host compartmental model to evaluate the effect of vaccination in the presence of antibody-dependent enhancement and cross-protection following recovery from primary infection. Reproducing the reported multi-annual patterns of dengue infection, our model projects that vaccination can dramatically reduce the overall incidence of the disease. However, if the duration of vaccine-induced protection is shorter than the average lifetime of the human population, vaccination can potentially increase the incidence of severe infection of dengue haemorrhagic fever due to the effects of antibody-dependent enhancement. The magnitude and timelines for this increase depend strongly on the efficacy and duration of the vaccine-induced protection. Corresponding to the current estimates of vaccine efficacy, we show that dengue eradication is infeasible using an imperfect vaccine. Furthermore, for a vaccine that induces lifetime protection, a nearly full coverage of infant vaccination is required for dengue elimination. Our findings suggest that other vector control measures may still play a significant role in dengue prevention even when a vaccine with high protection efficacy becomes available. PMID:26585748

  10. Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development.

    Science.gov (United States)

    Wilder-Smith, Annelies; Ooi, Eng-Eong; Vasudevan, Subhash G; Gubler, Duane J

    2010-05-01

    Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention. PMID:21308524

  11. Influenza-Specific Antibody-Dependent Phagocytosis

    OpenAIRE

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Stephen J Kent

    2016-01-01

    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, ...

  12. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

    Directory of Open Access Journals (Sweden)

    Jacky Flipse

    Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

  13. Dengue and Severe Dengue

    Science.gov (United States)

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Dengue and severe dengue Fact sheet Updated July 2016 Key facts Dengue ... risk of developing severe dengue. Global burden of dengue The incidence of dengue has grown dramatically around ...

  14. Current perspectives on dengue episode in Malaysia.

    Science.gov (United States)

    Pang, Ee Leen; Loh, Hwei-San

    2016-04-01

    Prevalence of dengue transmission has been alarmed by an estimate of 390 million infections per annum. Urban encroachment, ecological disruption and poor sanitation are all contributory factors of increased epidemiology. Complication however arises from the fact that dengue virus inherently exists as four different serotypes. Secondary infection is often manifested in the more severe form, such that antibody-dependent enhancement (ADE) could aggravate ailment by allowing pre-existing antibodies to form complexes with infecting viruses as means of intrusion. Consequently, increased viraemic titter and suppression of antiviral response are observed. Deep concerns are thus expressed in regards to escalating trend of hospitalisation and mortality rates. In Malaysia, situation is exacerbated by improper clinical management and pending vector control operations. As a preparedness strategy against the potential deadly dengue pandemic, the call for development of a durable and cost-effective dengue vaccine against all infecting serotypes is intensified. Even though several vaccine candidates are currently being evaluated in clinical trials, uncertainties in regards to serotypes interference, incomplete protection and dose adequacy have been raised. Instead of sole reliance on outsourcing, production of local vaccine should be considered in coherent to government's efforts to combat against dengue. PMID:27086160

  15. Laboratory-Enhanced Dengue Sentinel Surveillance in Colombo District, Sri Lanka: 2012-2014.

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    Hasitha Tissera

    2016-02-01

    Full Text Available Dengue has emerged as a significant public health problem in Sri Lanka. Historically surveillance was passive, with mandatory dengue notifications based on clinical diagnosis with only limited laboratory confirmation. To obtain more accurate data on the disease burden of dengue, we set up a laboratory-based enhanced sentinel surveillance system in Colombo District. Here we describe the study design and report our findings of enhanced surveillance in the years 2012-2014.Three outpatient clinics and three government hospitals in Colombo District that covered most of the Colombo metropolitan area were selected for the sentinel surveillance system. Up to 60 patients per week presenting with an undifferentiated fever were enrolled. Acute blood samples from each patient were tested by dengue specific PCR, NS1 ELISA and IgM ELISA. A sub-set of samples was sent to Duke-NUS Singapore for quality assurance, virus isolation and serotyping. Trained medical research assistants used a standardized case report form to record clinical and epidemiological data. Clinical diagnoses by the clinicians-in-charge were recorded for hospitalized cases.Of 3,127 febrile cases, 43.6% were PCR and/or NS1 positive for dengue. A high proportion of lab confirmed dengue was observed from inpatients (IPD (53.9% compared to outpatient (clinics in hospitals and general practice (7.6%. Dengue hemorrhagic fever (DHF was diagnosed in 11% of patients at the time of first contact, and the median day of illness at time of presentation to the sentinel sites was 4. Dengue serotype 1 was responsible for 85% of the cases and serotype 4 for 15%. The sensitivity and specificity of the clinicians' presumptive diagnosis of dengue was 84% and 34%, respectively.DENV-1, and to a lesser degree DENV-4, infection were responsible for a high proportion of febrile illnesses in Colombo in the years 2012 to 2014. Clinicians' diagnoses were associated with high sensitivity, but laboratory confirmation is

  16. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand.

  17. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. PMID:26645957

  18. Pathogenesis of Dengue: Dawn of a New Era [version 1; referees: 3 approved

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    Scott B. Halstead

    2015-11-01

    Full Text Available Dengue virus (DENV infections of humans were long thought to be self-limited and of low mortality. Beginning in the 1950s, at the time when four different DENVs were discovered, a lethal variant of dengue emerged. Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS initially observed in Southeast Asia now has spread throughout the world. Two risk factors for DHF/DSS are well-established: severe disease occurs during a second heterotypic DENV infection or during a first DENV infection in infants born to dengue-immune mothers. A large number of hypotheses have been proposed to explain severe dengue disease. As discussed, few of them attempt to explain why severe disease occurs under the two different immunological settings. New experimental evidence has demonstrated that DENV non-structural protein 1 (NS1 is toll-receptor 4 agonist that stimulates primary human myeloid cells to produce the same cytokines observed during the course of severe dengue disease. In addition, NS1 directly damages endothelial cells. These observations have been repeated and extended to an in vivo mouse model. The well-established phenomenon, antibody-dependent enhancement of DENV infection in Fc-receptor-bearing cells, should similarly enhance the production of DENV NS1 in humans, providing a unitary mechanism for severe disease in both immunological settings

  19. Dengue serotype immune-interactions and their consequences for vaccine impact predictions.

    Science.gov (United States)

    Lourenço, José; Recker, Mario

    2016-09-01

    Dengue is one of the most important and wide-spread viral infections affecting human populations. The last few decades have seen a dramatic increase in the global burden of dengue, with the virus now being endemic or near-endemic in over 100 countries world-wide. A recombinant tetravalent vaccine candidate (CYD-TDV) has recently completed Phase III clinical efficacy trials in South East Asia and Latin America and has been licensed for use in several countries. The trial results showed moderate-to-high efficacies in protection against clinical symptoms and hospitalisation but with so far unknown effects on transmission and infections per se. Model-based predictions about the vaccine's short- or long-term impact on the burden of dengue are therefore subject to a considerable degree of uncertainty. Furthermore, different immune interactions between dengue's serotypes have frequently been evoked by modelling studies to underlie dengue's oscillatory dynamics in disease incidence and serotype prevalence. Here we show how model assumptions regarding immune interactions in the form of antibody-dependent enhancement, temporary cross-immunity and the number of infections required to develop full immunity can significantly affect the predicted outcome of a dengue vaccination campaign. Our results thus re-emphasise the important gap in our current knowledge concerning the effects of previous exposure on subsequent dengue infections and further suggest that intervention impact studies should be critically evaluated by their underlying assumptions about serotype immune-interactions. PMID:27663790

  20. Dengue serotype immune-interactions and their consequences for vaccine impact predictions

    Directory of Open Access Journals (Sweden)

    José Lourenço

    2016-09-01

    Full Text Available Dengue is one of the most important and wide-spread viral infections affecting human populations. The last few decades have seen a dramatic increase in the global burden of dengue, with the virus now being endemic or near-endemic in over 100 countries world-wide. A recombinant tetravalent vaccine candidate (CYD-TDV has recently completed Phase III clinical efficacy trials in South East Asia and Latin America and has been licensed for use in several countries. The trial results showed moderate-to-high efficacies in protection against clinical symptoms and hospitalisation but with so far unknown effects on transmission and infections per se. Model-based predictions about the vaccine's short- or long-term impact on the burden of dengue are therefore subject to a considerable degree of uncertainty. Furthermore, different immune interactions between dengue's serotypes have frequently been evoked by modelling studies to underlie dengue's oscillatory dynamics in disease incidence and serotype prevalence. Here we show how model assumptions regarding immune interactions in the form of antibody-dependent enhancement, temporary cross-immunity and the number of infections required to develop full immunity can significantly affect the predicted outcome of a dengue vaccination campaign. Our results thus re-emphasise the important gap in our current knowledge concerning the effects of previous exposure on subsequent dengue infections and further suggest that intervention impact studies should be critically evaluated by their underlying assumptions about serotype immune-interactions.

  1. Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

    OpenAIRE

    Meng Ling Moi; Chang-Kweng Lim; Kaw Bing Chua; Tomohiko Takasaki; Ichiro Kurane

    2012-01-01

    BACKGROUND: Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enha...

  2. Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

    OpenAIRE

    Moi, Meng Ling; Lim, Chang-Kweng; Chua, Kaw Bing; Takasaki, Tomohiko; Kurane, Ichiro

    2012-01-01

    Background Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhan...

  3. Dengue Epidemiology

    Science.gov (United States)

    ... and dengue shock syndrome (DSS). Transmission of the Dengue Virus Dengue is transmitted between people by the ... the vectors is too infrequent to sustain transmission. Dengue is an Emerging Disease The four dengue viruses ...

  4. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    Directory of Open Access Journals (Sweden)

    Scott R Fry

    2011-06-01

    Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

  5. Modeled Forecasts of Dengue Fever in San Juan, Puerto Rico Using NASA Satellite Enhanced Weather Forecasts

    Science.gov (United States)

    Morin, C.; Quattrochi, D. A.; Zavodsky, B.; Case, J.

    2015-12-01

    Dengue fever (DF) is an important mosquito transmitted disease that is strongly influenced by meteorological and environmental conditions. Recent research has focused on forecasting DF case numbers based on meteorological data. However, these forecasting tools have generally relied on empirical models that require long DF time series to train. Additionally, their accuracy has been tested retrospectively, using past meteorological data. Consequently, the operational utility of the forecasts are still in question because the error associated with weather and climate forecasts are not reflected in the results. Using up-to-date weekly dengue case numbers for model parameterization and weather forecast data as meteorological input, we produced weekly forecasts of DF cases in San Juan, Puerto Rico. Each week, the past weeks' case counts were used to re-parameterize a process-based DF model driven with updated weather forecast data to generate forecasts of DF case numbers. Real-time weather forecast data was produced using the Weather Research and Forecasting (WRF) numerical weather prediction (NWP) system enhanced using additional high-resolution NASA satellite data. This methodology was conducted in a weekly iterative process with each DF forecast being evaluated using county-level DF cases reported by the Puerto Rico Department of Health. The one week DF forecasts were accurate especially considering the two sources of model error. First, weather forecasts were sometimes inaccurate and generally produced lower than observed temperatures. Second, the DF model was often overly influenced by the previous weeks DF case numbers, though this phenomenon could be lessened by increasing the number of simulations included in the forecast. Although these results are promising, we would like to develop a methodology to produce longer range forecasts so that public health workers can better prepare for dengue epidemics.

  6. Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever.

    Science.gov (United States)

    Chanthick, Chanettee; Kanlaya, Rattiyaporn; Kiatbumrung, Rattanaporn; Pattanakitsakul, Sa-Nga; Thongboonkerd, Visith

    2016-01-01

    Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between "paracellular" endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether "transcellular" endothelial leakage is involved in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) remained unknown. We thus investigated effects of DENV (serotype 2) infection on transcellular transport of albumin, the main oncotic plasma protein, through human endothelial cell monolayer by Western blotting, immunofluorescence staining, fluorescence imaging, and fluorometry. The data showed that Alexa488-conjugated bovine serum albumin (Alexa488-BSA) was detectable inside DENV2-infected cells and its level was progressively increased during 48-h post-infection. While paracellular transport could be excluded using FITC-conjugated dextran, Alexa488-BSA was progressively increased and decreased in lower and upper chambers of Transwell, respectively. Pretreatment with nystatin, an inhibitor of caveolae-dependent endocytic pathway, significantly decreased albumin internalization into the DENV2-infected cells, whereas inhibitors of other endocytic pathways showed no significant effects. Co-localization of the internalized Alexa488-BSA and caveolin-1 was also observed. Our findings indicate that DENV infection enhances caveolae-mediated albumin transcytosis through human endothelial cells that may ultimately induce plasma leakage from intravascular compartment. Further elucidation of this model in vivo may lead to effective prevention and better therapeutic outcome of DHF/DSS. PMID:27546060

  7. Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses

    OpenAIRE

    Chen-Yi Chiang; Ming-Hsi Huang; Chun-Hsiang Hsieh; Mei-Yu Chen; Hsueh-Hung Liu; Jy-Ping Tsai; Yi-Shiuan Li; Ching-Yun Chang; Shih-Jen Liu; Pele Chong; Chih-Hsiang Leng; Hsin-Wei Chen

    2012-01-01

    Author Summary Dengue is a mosquito-borne disease. Infection of dengue virus can cause clinical manifestations ranging from self-limiting dengue fever to potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. In recent years, dengue has spread to most tropical and subtropical areas, making it a global health concern. Specific approaches for dengue therapy do not exist; the development of a dengue vaccine would represent a major advance in the control of the disease. C...

  8. Human apolipoprotein A-I is associated with dengue virus and enhances virus infection through SR-BI.

    Directory of Open Access Journals (Sweden)

    Yujia Li

    Full Text Available Diseases caused by dengue virus (DV infection vary in severity, with symptoms ranging from mild fever to life threatening dengue hemorrhage fever (DHF and dengue shock syndrome (DSS. Clinical studies have shown that significant decrease in the level of lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that lipoproteins including high-density lipoprotein (HDL and low-density lipoprotein (LDL are able to facilitate cell entry of HCV or other flaviviruses via corresponding lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that apolipoprotein A-I (ApoA-I, the major protein component in HDL, is associated with DV particles and is able to promote DV infection. Based on that observation, we further found that siRNA knockdown of the scavenger receptor class B type I (SR-BI, the cell receptor of ApoA-I, abolished the activity of ApoA-I in enhancement of DV infection. This suggests that ApoA-I bridges DV particles and cell receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface dengue antigen after virus absorption further confirmed that ApoA-I enhances DV infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of lipoproteins in dengue pathogenesis.

  9. Heterotypic Dengue Infection with Live Attenuated Monotypic Dengue Virus Vaccines: Implications for Vaccination of Populations in Areas Where Dengue Is Endemic

    OpenAIRE

    Durbin, Anna P.; Schmidt, Alexander; Elwood, Dan; Wanionek, Kimberli A.; Lovchik, Janece; Thumar, Bhavin; Murphy, Brian R.; Whitehead, Stephen S.

    2011-01-01

    Background. Because infection with any of the 4 Dengue virus serotypes may elicit both protective neutralizing antibodies and nonneutralizing antibodies capable of enhancing subsequent heterotypic Dengue virus infections, the greatest risk for severe dengue occurs during a second, heterotypic Dengue virus infection. It remains unclear whether the replication of live attenuated vaccine viruses will be similarly enhanced when administered to Dengue-immune individuals.

  10. Modeled Forecasts of Dengue Fever in San Juan, PR Using NASA Satellite Enhanced Weather Forecasts

    Science.gov (United States)

    Morin, Cory; Quattrochi, Dale; Zavodsky, Bradley; Case, Jonathan

    2015-01-01

    Dengue virus is transmitted between humans and mosquitoes of the genus Aedes and causes approximately 96 million cases of disease (dengue fever) each year (Bhatet al. 2013). Symptoms of dengue fever include fever, headache, nausea, vomiting, and eye, muscle and joint pain (CDC). More sever manifestations such as abdominal pain, bleeding from nose and gums, vomiting of blood, and clammy skin occur in rare cases of dengue hemorrhagic fever (CDC). Dengue fever occurs throughout tropical and sub-tropical regions worldwide, however, the geographical range and size of epidemics is increasing. Weather and climate are drivers of dengue virus transmission dynamics (Morin et al. 2013) by affecting mosquito proliferation and the virus extrinsic incubation period (i.e. required time for the virus to replicate and disseminate within the mosquito before it can retransmit the virus).

  11. Advances in the development of vaccines for dengue fever

    Directory of Open Access Journals (Sweden)

    Simmons M

    2012-05-01

    Full Text Available Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV serotypes 1–4, and is the most common arboviral infection of humans in subtropical and tropical regions of the world. There are currently no prophylaxis or treatment options in the form of vaccines or antivirals, leaving vector control the only method of prevention. A particular challenge with DENV is that a successful vaccine has to be effective against all four serotypes without predisposing for antibody-mediated enhanced disease. In this review, we discuss the current lead vaccine candidates in clinical trials, as well as some second-generation vaccine candidates undergoing preclinical evaluation. In addition, we discuss DENV epidemiology, clinical disease and strategies used for Flavivirus antivirals in the past, the development of new DENV therapeutics, and their potential usefulness for prophylaxis and treatment.Keywords: tetravalent dengue vaccine, live attenuated vaccine, purified inactivated vaccine, DNA vaccine, antibody-dependent enhancement, antivirals

  12. High pro-inflammatory cytokine secretion and loss of high avidity cross-reactive cytotoxic T-cells during the course of secondary dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Tao Dong

    Full Text Available BACKGROUND: Dengue is one of the most important human diseases transmitted by an arthropod vector and the incidence of dengue virus infection has been increasing - over half the world's population now live in areas at risk of infection. Most infections are asymptomatic, but a subset of patients experience a potentially fatal shock syndrome characterised by plasma leakage. Severe forms of dengue are epidemiologically associated with repeated infection by more than one of the four dengue virus serotypes. Generally attributed to the phenomenon of antibody-dependent enhancement, recent observations indicate that T-cells may also influence disease phenotype. METHODS AND FINDINGS: Virus-specific cytotoxic T lymphocytes (CTL showing high level cross reactivity between dengue serotypes could be expanded from blood samples taken during the acute phase of secondary dengue infection. These could not be detected in convalescence when only CTL populations demonstrating significant serotype specificity were identified. Dengue cross-reactive CTL clones derived from these patients were of higher avidity than serotype-specific clones and produced much higher levels of both type 1 and certain type 2 cytokines, many previously implicated in dengue pathogenesis. CONCLUSION: Dengue serotype cross-reactive CTL clones showing high avidity for antigen produce higher levels of inflammatory cytokines than serotype-specific clones. That such cells cannot be expanded from convalescent samples suggests that they may be depleted, perhaps as a consequence of activation-induced cell death. Such high avidity cross-reactive memory CTL may produce inflammatory cytokines during the course of secondary infection, contributing to the pathogenesis of vascular leak. These cells appear to be subsequently deleted leaving a more serotype-specific memory CTL pool. Further studies are needed to relate these cellular observations to disease phenotype in a large group of patients. If

  13. Mouse models of dengue virus infection for vaccine testing.

    Science.gov (United States)

    Sarathy, Vanessa V; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-12-10

    Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple

  14. Dengue Virus Nonstructural Protein 1-Induced Antibodies Cross-React with Human Plasminogen and Enhance Its Activation.

    Science.gov (United States)

    Chuang, Yung-Chun; Lin, Jessica; Lin, Yee-Shin; Wang, Shuying; Yeh, Trai-Ming

    2016-02-01

    Dengue virus (DENV) infection is the most common mosquito-borne viral disease, and it can cause life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks of DHF/DSS. However, the mechanism underlying hemorrhage in DHF/DSS remains elusive. In previous studies, plasminogen (Plg) cross-reactive Abs, which can recognize DENV nonstructural protein (NS) 1, have been found in dengue patients. However, it is unclear whether these Abs are indeed induced by DENV NS1. Thus, we immunized mice with recombinant NS1 from both bacteria and drosophila to determine whether NS1 can induce Plg cross-reactive Abs. The results from the NS1-immunized mouse sera indicated that NS1 immunization induced Abs that could cross-react with Plg. To study the effects of these NS1-induced Plg cross-reactive Abs on fibrinolysis, we isolated several Plg cross-reactive anti-NS1 mAbs from these mice and found that some of them could enhance Plg activation. In addition, epitope mapping with a phage-displayed random peptide library revealed that one of these mAbs (2A5) could recognize NS1 C-terminal residues 305-311, which share sequence homology with Plg residues 590-597. A synthetic peptide of NS1 residues 305-311 could inhibit the binding of both 2A5 and its Fab to Plg and its enhanced activation. Thus, our results suggest that DENV NS1 can induce Plg cross-reactive Abs through molecular mimicry, which can enhance Plg activation and may contribute to the pathogenesis of DHF/DSS. PMID:26712948

  15. [Dengue fever: from disease to vaccination].

    Science.gov (United States)

    Teyssou, R

    2009-08-01

    Dengue is a tropical disease affecting 110 countries throughout the world and placing over 3 billion people at risk of infection. According the World Health Organization 70 to 500 million persons are infected every year including 2 million who develop hemorrhagic form and 20,000 who die. Children are at highest risk for death. Due to the absence of specialized laboratories in most endemic regions and to the lack of specifici clinical presentation, the incidence of dengue and its economic costs are certainly underestimated. Dengue iscaused by an arbovirus belonging to the Flavivirus genus of the family Flaviviridae. There are four dengue virus serotypes and no cross protection between them. The disease is transmitted through the bites of mosquitoes belonging to the Aedes genus, mainly Aedes aegypti. However A. albopictus has played an important role in the spread of the disease and other species may be involved in specific locations (e.g., A. polynesiensis in the South Pacific). There is no specific treatment for dengue. Management of severe forms depends on symptomatic treatment of hemorrhagic complications and hypovolemic shock. Prevention requires control of vector mosquitoes that is difficult to implement and maintain. Dengue is a major emerging infectious disease with a heavy impact on public health. The high human and economic costs as well as the absence of specific preventive measures underscore the need to develop a vaccine. However finding and distributing such a vaccine to populations at risk is hampered by numerous obstacles. The most notable challenges standing in the way of development of a candidate vaccine are as follows: absence of an animal model, which has important implications for the preclinical development strategy; need to develop a live attenuated vaccine; existence of 4 antigenically distinct serotypes with the resulting risk of competition between vaccine strains; immunologic risks related to antibody-dependent enhancement that has been

  16. Dengue encephalitis

    OpenAIRE

    Kapil Borawake; Parikshit Prayag; Atul Wagh; Swati Dole

    2011-01-01

    We report a case of dengue fever with features of encephalitis. The diagnosis of dengue was confirmed by the serum antibodies to dengue and the presence of a dengue antigen in the cerebrospinal fluid. This patient had characteristic magnetic resonance imaging brain findings, mainly involving the bilateral thalami, with hemorrhage. Dengue is not primarily a neurotropic virus and encephalopathy is a common finding in Dengue. Hence various other etiological possibilities were considered before c...

  17. Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells.

    Science.gov (United States)

    Alayli, Farah; Scholle, Frank

    2016-09-01

    Dengue virus (DV) has become the most prevalent arthropod borne virus due to globalization and climate change. It targets dendritic cells during infection and leads to production of pro-inflammatory cytokines and chemokines. Several DV non-structural proteins (NS) modulate activation of human dendritic cells. We investigated the effect of DV NS1 on human monocyte-derived dendritic cells (mo-DCs) during dengue infection. NS1 is secreted into the serum of infected individuals where it interacts with various immune mediators and cell types. We purified secreted DV1 NS1 from supernatants of 293T cells that over-express the protein. Upon incubation with mo-DCs, we observed NS1 uptake and enhancement of early DV1 replication. As a consequence, mo-DCs that were pre-exposed to NS1 produced more pro-inflammatory cytokines in response to subsequent DV infection compared to DCs exposed to heat-inactivated NS1 (HNS1). Therefore the presence of exogenous NS1 is able to modulate dengue infection in mo-DCs. PMID:27348054

  18. Antibody-dependent cellular cytotoxicity and skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Norris, D.A.; Lee, L.A.

    1985-07-01

    Antibody dependent cellular cytotoxicity (ADCC) is a recently described mechanism of immunologic lysis in which cellular targets sensitized by specific antibodies are efficiently and selectively lysed by Fc receptor (FcR) bearing nonspecific effectors. Immunoglobulins of various classes (IgG, IgM, IgA, IgE) and various cellular effectors (large granular lymphocytes, monocyte/macrophages, T lymphocytes, neutrophils, and eosinophils) can induce ADCC in vitro, and the importance of ADCC in vivo is being tested experimentally in resistance to viral, bacterial, and parasitic infection, in tumor surveillance, in allograft rejection, and in inflammatory diseases. There is much indirect evidence that ADCC may be the mechanism of damage of different cellular targets in skin diseases, but the best direct evidence concerns immunologic keratinocyte damage, especially in cutaneous lupus erythematosus (LE). The authors have shown that keratinocytes of several species are highly susceptible to lymphocyte and monocyte-mediated ADCC, but not to neutrophil or eosinophil ADCC in vitro using two different cytotoxicity assays. In contrast, complement was a relatively ineffective mediator of lysis of metabolically intact keratinocyte targets. Patients with certain cutaneous lupus syndromes have serum antibodies capable of inducing monocyte and lymphocyte ADCC of targets coated with extractable nuclear antigens. The authors have shown that these antigens apparently move to the cell membrane of keratinocytes in vitro following ultraviolet irradiation. In an animal model, they have shown that antibodies to SSA/Ro bind to human keratinocytes in vivo, especially after ultraviolet irradiation.

  19. Dengue Fever

    Science.gov (United States)

    ... A Text Size What's in this article? About Dengue Fever Signs & Symptoms Diagnosis Treatment Prevention en español Fiebre del dengue Dengue fever is ... the illness from spreading to others. previous continue Prevention There is no vaccine to prevent dengue fever, so if children live in or will ...

  20. 登革病毒包膜蛋白疫苗的研究进展%Study Progress on Dengue Vaccine Based on Envelope Protein

    Institute of Scientific and Technical Information of China (English)

    李雪玲

    2012-01-01

    Dengue is a mosquito-borne viral disease, caused by four antigenically distinct serotypes of dengue viruses which can result in illness ranging from a mild fever to hemorrhaging, shock, or even death. Currently there are no approved vaccines preventing dengue. Cross-protection between dengue virus serotype is limited and antibody dependent enhancement contributes significantly to the severity of the disease. The major challenge is to induce a broad durable immune response against all four serotypes of dengue virus simultaneously. Most strategies for the development of dengue vaccine focused on the envelope protein of dengue virus. The recent developments of dengue vaccines based on envelope protein are discussed in the articles.%登革热由登革病毒引起,有时会发生更严重的登革出血热和登革休克综合征,严重威胁人类的健康.登革病毒疫苗的研究已有50多年的历史,迄今仍无有效的疫苗被批准使用.病情加重的发病机制可能与抗体依赖的增强作用有关,理想的登革疫苗是对四种血清型登革病毒都具有保护作用.包膜蛋白是登革病毒的主要抗原,现以包膜蛋白为目的抗原的登革疫苗的研究作一综述.

  1. Evasion of the human innate immune system by dengue virus

    OpenAIRE

    Pagni, Sarah; Fernandez-Sesma, Ana

    2012-01-01

    Dengue virus is a worldwide health problem, with billions of people at risk annually. Dengue virus causes a spectrum of diseases, namely dengue fever, dengue hemorrhagic fever and dengue shock syndrome with the latter two being linked to death. Understanding how dengue is able to evade the immune system and cause enhanced severity of disease is the main topics of interest in the Fernandez-Sesma laboratory at Mount Sinai School of Medicine. Using primary human immune cells, our group investiga...

  2. Dengue Prevention

    Science.gov (United States)

    ... Think You Have Dengue Epidemiology Entomology/Ecology Mosquito Life-Cycle Mosquito Aquatic Habitats Dengue And Climate Clinical/Laboratory ... find indoors and wear repellent! List of repellant products approved by the EPA : http://cfpub.epa.gov/ ...

  3. An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2.

    Directory of Open Access Journals (Sweden)

    Chung-Tao Tang

    Full Text Available Dengue virus (DENV, a global disease, is divided into four serotypes (DENV1-4. Cross-reactive and non-neutralizing antibodies against envelope (E protein of DENV bind to the Fcγ receptors (FcγR of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE. Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines.

  4. Dengue hemorrhagic fever

    Science.gov (United States)

    Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever ... Four different dengue viruses are known to cause dengue hemorrhagic fever. Dengue hemorrhagic fever occurs when a person is bitten by ...

  5. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    OpenAIRE

    Fry, Scott R.; Michelle Meyer; Semple, Matthew G.; Cameron P Simmons; Shamala Devi Sekaran; Huang, Johnny X.; Catriona McElnea; Chang-Yi Huang; Andrea Valks; Paul R. Young; Cooper, Matthew A.

    2011-01-01

    BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early...

  6. The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

    OpenAIRE

    Fry, Scott R.; Meyer, Michelle; Semple, Matthew G.; Cameron P. Simmons; Sekaran, Shamala Devi; Johnny X. Huang; McElnea, Catriona; Huang, Chang-Yi; Valks, Andrea; Young, Paul R.; Cooper, Matthew A.

    2011-01-01

    Background Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1–9 post-onset of illness but following seroconversion it can be difficult to detect in serum. Aims To evaluate the performance of a newly developed Panbio® Dengue Early R...

  7. Fc-galactosylation modulates antibody-dependent cellular cytotoxicity of therapeutic antibodies.

    Science.gov (United States)

    Thomann, Marco; Reckermann, Katharina; Reusch, Dietmar; Prasser, Jessica; Tejada, Max L

    2016-05-01

    The therapeutic activity of monoclonal antibodies can involve immune cell mediated effector functions including antibody-dependent cellular cytotoxicity (ADCC), an activity that is modulated by the structure of Fc-glycans, and in particular the lack of core fucose. The heterogeneity of these glycostructures and the inherent variability of traditional PBMC-based in vitro ADCC assays, have made it challenging to quantitatively assess the impact of other glycostructures on ADCC activity. We applied a quantitative NK cell based assay to generate a database consisting of Fc-glycostructure and ADCC data from 54 manufacturing batches of a CHO-derived monoclonal antibody. Explorative analysis of the data indicated that, apart from afucosylation, galactosylation levels could influence ADCC activity. We confirmed this hypothesis by demonstrating enhanced ADCC upon enzymatic hypergalactosylation of four different monoclonal antibodies derived using standard CHO manufacturing processes. Furthermore we quantitatively compare the effects of galactosylation and afucosylation in the context of glycan heterogeneity and demonstrate that while galactose can influence ADCC activity, afucosylation remains the primary driver of this activity. PMID:27058641

  8. CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes

    Science.gov (United States)

    Yeap, Wei Hseun; Wong, Kok Loon; Shimasaki, Noriko; Teo, Esmeralda Chi Yuan; Quek, Jeffrey Kim Siang; Yong, Hao Xiang; Diong, Colin Phipps; Bertoletti, Antonio; Linn, Yeh Ching; Wong, Siew Cheng

    2016-01-01

    Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16− expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies. Engagement of CD16 on monocytes by antibody bound to target cells activated β2-integrins and induced TNFα secretion. In turn, this induced TNFR expression on the target cells, making them susceptible to TNFα-mediated cell death. Treatment with TLR agonists, DAMPs or cytokines, such as IFNγ, further enhanced ADCC. Monocytes lacking CD16 did not exert ADCC but acquired this property after CD16 expression was induced by either cytokine stimulation or transient transfection. Notably, CD16+ monocytes from patients with leukemia also exerted potent ADCC. Hence, CD16+ monocytes are important effectors of ADCC, suggesting further developments of this property in the context of cellular therapies for cancer and infectious diseases. PMID:27670158

  9. An improved assay for antibody dependent cellular cytotoxicity based on time resolved fluorometry.

    Science.gov (United States)

    Patel, A K; Boyd, P N

    1995-07-17

    A new and faster assay for antibody dependent cellular cytotoxicity based on release of europium from target cells is described. This has a number of important advantages over the traditional assays based on release of chromium-51 (51Cr). The new method involves labelling of Wein 133 target cells (B cell non-Hodgkin's lymphoma cells) which express the antigen, CDw52, with the chelate europium diethylenetriaminopentaacetic acid (EuDTPA) according to the method of Blomberg et al. (1986). Labelled cells are sensitised (coated) with the anti-lymphocytic monoclonal antibody, Campath-1H. Human peripheral blood mononuclear cells are added to mediate lysis of EuDTPA labelled Wein 133 cells by ADCC. Release of EuDTPA from lysed cells is determined by mixing supernatants with enhancement solution containing 2-naphthoyl trifluoroacetone, 2-NTA, to form a highly fluorescent chelate which is measured using time resolved fluorometry. Results obtained with the new EuDPTA release assays were comparable to traditional assays based on the release of the radioisotope 51Cr. It is anticipated that this assay will have a widespread application among laboratories performing ADCC assays. The method is non-hazardous and has been used routinely for over 2 years to monitor production and purification of Campath-1H. PMID:7622867

  10. Dengue and Dengue Hemorrhagic Fever

    OpenAIRE

    Gubler, Duane J.

    1998-01-01

    Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000...

  11. A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity.

    Science.gov (United States)

    Wu, Yuling; Li, Jia J; Kim, Hyun Jun; Liu, Xu; Liu, Weiyi; Akhgar, Ahmad; Bowen, Michael A; Spitz, Susan; Jiang, Xu-Rong; Roskos, Lorin K; White, Wendy I

    2015-11-01

    Benralizumab is a humanized anti-IL5 receptor α (IL5Rα) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody (NAb) assay was developed and characterized to detect NAb against benralizumab in human serum to support the clinical development of benralizumab. The optimal ratio of target cells to effector cells was 3:1. Neither parental benralizumab (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the requirement for ADCC activity in the NAb assay. The serum tolerance of the cells was determined to be 2.5%. The cut point derived from normal and asthma serum samples was comparable. The effective range of benralizumab was determined, and 35 ng/mL [80% maximal effective concentration (EC80)] was chosen as the standard concentration to run in the assessment of NAb. An affinity purified goat anti-benralizumab polyclonal idiotype antibody preparation was shown to have NAb since it inhibited ADCC activity in a dose-dependent fashion. The low endogenous concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to interfere with the assay. The estimated assay sensitivities at the cut point were 1.02 and 1.10 μg/mL as determined by the surrogate neutralizing goat polyclonal and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay can detect NAb (at 2.5 μg/mL) in the presence of 0.78 μg/mL benralizumab. The assay was not susceptible to non-specific matrix effects. This study provides an approach and feasibility of developing an ADCC cell-based NAb assay to support biopharmaceuticals with an ADCC function. PMID:26205082

  12. Reemergence of Dengue in Southern Texas, 2013.

    Science.gov (United States)

    Thomas, Dana L; Santiago, Gilberto A; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Smith, Brian; Banicki, Alison; Tomashek, Kay M; Gaul, Linda; Sharp, Tyler M

    2016-06-01

    During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico. PMID:27191223

  13. Reemergence of Dengue in Southern Texas, 2013.

    Science.gov (United States)

    Thomas, Dana L; Santiago, Gilberto A; Abeyta, Roman; Hinojosa, Steven; Torres-Velasquez, Brenda; Adam, Jessica K; Evert, Nicole; Caraballo, Elba; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Smith, Brian; Banicki, Alison; Tomashek, Kay M; Gaul, Linda; Sharp, Tyler M

    2016-06-01

    During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico.

  14. Dengue-1 envelope protein domain III along with PELC and CpG oligodeoxynucleotides synergistically enhances immune responses.

    Directory of Open Access Journals (Sweden)

    Chen-Yi Chiang

    Full Text Available The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus.

  15. Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

    DEFF Research Database (Denmark)

    Hokland, P; Hokland, M; Ellegaard, J

    1981-01-01

    This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunolog...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...... techniques including detection of ALL antigens and terminal transferase. The malignant cells were subsequently found to be potent effectors in NK and ADCC assays. Addition of partially purified alpha-interferon to the in vitro cultures was found to have an enhancing effect on NK activity, whereas...

  16. Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcγR-expressing cells.

    Directory of Open Access Journals (Sweden)

    Meng Ling Moi

    Full Text Available BACKGROUND: Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhancing activity, may better reflect the biological properties of antibodies in vivo. METHODS AND FINDINGS: We evaluated serum samples from 80 residents of a dengue endemic country, Malaysia, for neutralizing activity, and infection-enhancing activity at 1∶10 serum dilution by using FcγR-negative BHK cells and FcγR-expressing BHK cells. The serum samples consisted of a panel of patients with acute DENV infection (31%, 25/80 and a panel of donors without acute DENV infection (69%, 55/80. A high proportion of the tested serum samples (75%, 60/80 demonstrated DENV neutralizing activity (PRNT(50≥10 and infection-enhancing activity. Eleven of 18 serum samples from patients with acute secondary DENV infection demonstrated neutralizing activity to the infecting serotype determined by using FcγR-negative BHK cells (PRNT(50≥10, but not when determined by using FcγR-expressing cells. CONCLUSION: Human serum samples with low neutralizing activity determined by using FcγR-negative cells showed DENV infection-enhancing activity using FcγR-expressing cells, whereas those with high neutralizing activity determined by using FcγR-negative cells demonstrate low or no infection-enhancing activity using FcγR-expressing cells. The results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity, and that neutralizing activity determined by using FcγR-expressing cells, and not the activity determined by using Fc

  17. Dengue fever

    Science.gov (United States)

    Clothing, mosquito repellent, and netting can help reduce the risk of mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they ...

  18. Dengue Returns

    Centers for Disease Control (CDC) Podcasts

    2016-08-25

    Dr. Tyler Sharp, a CDC epidemiologist, discusses dengue in southern Texas.  Created: 8/25/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/25/2016.

  19. Oxygen dependence of human alveolar macrophage-mediated antibody-dependent cytotoxicity.

    OpenAIRE

    Conkling, P.; Papermaster-Bender, G; Whitcomb, M; Sagone, A L

    1982-01-01

    We studied the metabolic characteristics of the human alveolar macrophage-mediated antibody-dependent cytotoxicity (ADCC) reaction, using an anti-D sensitized human erythrocyte target system. Metabolic experiments demonstrated a high resting rate of glucose metabolism in macrophages, but no oxidative metabolic burst was found to accompany the ADCC reaction. These findings were confirmed by oxygen consumption studies, showing a high resting rate of oxygen consumption by macrophages, but no cha...

  20. Activation of Monocyte and Granulocyte Antibody-Dependent Cytotoxicity by Phorbol Myristate Acetate

    OpenAIRE

    Klassen, David K.; Conkling, Paul R.; Sagone, Arthur L.

    1982-01-01

    We have characterized the effects of phorbol myristate acetate (PMA) on human monocyte and neutrophil oxidative metabolism and antibody-dependent cytotoxicity toward anti-D sensitized human erythrocytes (RBC) and a human lymphoblastoid cell line (CEM). Hexose monophosphate shunt activity was measured by [1-14C]glucose oxidation and target lysis by 51Cr release. PMA produced a dose-dependent stimulation of hexose monophosphate shunt activity. Neutrophils responded with higher hexose monophosph...

  1. Dengue Fever: Causes, Complications, and Vaccine Strategies.

    Science.gov (United States)

    Khetarpal, Niyati; Khanna, Ira

    2016-01-01

    Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur's chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals. PMID:27525287

  2. Dengue Fever: Causes, Complications, and Vaccine Strategies

    Science.gov (United States)

    Khanna, Ira

    2016-01-01

    Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur's chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals. PMID:27525287

  3. Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

    Directory of Open Access Journals (Sweden)

    Trai-Ming Yeh

    Full Text Available Dengue virus (DV infections cause mild dengue fever (DF or severe life-threatening dengue hemorrhagic fever (DHF. The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM and macrophage migration inhibitory factor (MIF are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM and intercellular adhesion molecule-1 (ICAM-1 in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

  4. Seroprevalence of dengue virus antibodies in healthy Jamaicans.

    Science.gov (United States)

    Brown, Michelle G; Vickers, Ivan E; Salas, Rose Alba; Smikle, Monica F

    2009-01-01

    Dengue fever, a mosquito borne viral infection, is endemic to Jamaica. The seroprevalence of dengue IgG and IgM antibodies were determined in 277 healthy Jamaicans by enzyme linked immunosorbent assay (ELISA). The seroprevalence of dengue IgG antibodies was 100% (277/277) while dengue IgM antibodies were found in 3.6% (10/277). A statistically significant association was found between the presence of dengue IgM antibodies and gender (males 10/105, 9.5% vs females 0/172, 0.0%); chi(2) = 17.0, p=0.000.The high seroprevalence rate of dengue IgG antibodies and the presence of dengue IgM in the healthy population are in keeping with the endemicity of the virus in Jamaica. Therefore tests for dengue IgG antibodies are of limited usefulness in Jamaica and can be safely excluded from diagnostic testing as a cost saving measure. Serological diagnosis of current dengue infection should be centred around the dengue IgM tests although the limitations in the predictive values of such tests should also be considered. The results also suggest that the risk of emergence of the more severe forms of dengue, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) in the Jamaican population, due to the presence of enhancing antibodies, is high. PMID:19996526

  5. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S.

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  6. Screening of anti-dengue activity in methanolic extracts of medicinal plants

    Directory of Open Access Journals (Sweden)

    Tang Leon IC

    2012-01-01

    Full Text Available Abstract Background Dengue fever regardless of its serotypes has been the most prevalent arthropod-borne viral diseases among the world population. The development of a dengue vaccine is complicated by the antibody-dependent enhancement effect. Thus, the development of a plant-based antiviral preparation promises a more potential alternative in combating dengue disease. Methods Present studies investigated the antiviral effects of standardised methanolic extracts of Andrographis paniculata, Citrus limon, Cymbopogon citratus, Momordica charantia, Ocimum sanctum and Pelargonium citrosum on dengue virus serotype 1 (DENV-1. Results O. sanctum contained 88.6% of total flavonoids content, an amount that was the highest among all the six plants tested while the least was detected in M. charantia. In this study, the maximum non-toxic dose (MNTD of the six medicinal plants was determined by testing the methanolic extracts against Vero E6 cells in vitro. Studies also determined that the MNTD of methanolic extract was in the decreasing order of M. charantia >C. limon >P. citrosum, O. sanctum >A. paniculata >C. citratus. Antiviral assay based on cytopathic effects (CPE denoted by degree of inhibition upon treating DENV1-infected Vero E6 cells with MNTD of six medicinal plants showed that A. paniculata has the most antiviral inhibitory effects followed by M. charantia. These results were further verified with an in vitro inhibition assay using MTT, in which 113.0% and 98.0% of cell viability were recorded as opposed to 44.6% in DENV-1 infected cells. Although methanolic extracts of O. sanctum and C. citratus showed slight inhibition effect based on CPE, a significant inhibition was not reflected in MTT assay. Methanolic extracts of C. limon and P. citrosum did not prevent cytopathic effects or cell death from DENV-1. Conclusions The methanol extracts of A. paniculata and M. charantia possess the ability of inhibiting the activity of DENV-1 in in vitro assays

  7. Dengue Fever Treatment

    Science.gov (United States)

    ... Volunteer NIAID > Health & Research Topics > Dengue Fever > Understanding Dengue Fever Understanding Cause Transmission Symptoms Diagnosis Treatment Prevention Complications Research Skip Website Tools Website Tools Print ...

  8. Generation of Anti-platelet Autoantibody During Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Huan-Yao Lei

    2008-01-01

    Full Text Available Dengue virus infection causes dengue fever, Dengue Hemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS. Thrombocytopenia is common in dengue fever and is always found in DHF/DSS. The pathogenesis of thrombocytopenia is poorly understood. To further understand the relationship between anti-dengue virus antibody and anti-platelet antibody, we generated monoclonal anti-dengue virus antibodies from the dengue virus infected mice that developed transient thrombocytopenia post dengue infection. The analysis of a panel of monoclonal anti-NS-1 antibodies reveals three different patterns of platelet binding: strong, intermediate, or dull. Their isotypes are different, some are IgM while others are IgG1. Most of anti-platelet antibodies are cross-reactive with NS-1 of dengue virus and can be competitively inhibited by recombinant NS-1 protein, suggesting a molecular mimicry between dengue virus NS-1 protein and platelet. A clone, 13-F4-G5, preferentially bound activated platelets, can recognize two or three proteins around 150 kD on platelets. The binding to platelet would lyse the platelet in the presence of complement or enhance the ADP-induced platelet aggregation. Furthermore, some of these monoclonal antibodies would also react with the cellular antigens of BHK. Based on the data, we conclude that dengue virus infection induces auto anti-platelet antibodies which thereafter may involve in the manifestation of thrombocytopenia. A molecular mimicry between NS-1 and platelet is demonstrated.

  9. Optimal lead time for dengue forecast.

    Directory of Open Access Journals (Sweden)

    Yien Ling Hii

    Full Text Available BACKGROUND: A dengue early warning system aims to prevent a dengue outbreak by providing an accurate prediction of a rise in dengue cases and sufficient time to allow timely decisions and preventive measures to be taken by local authorities. This study seeks to identify the optimal lead time for warning of dengue cases in Singapore given the duration required by a local authority to curb an outbreak. METHODOLOGY AND FINDINGS: We developed a Poisson regression model to analyze relative risks of dengue cases as functions of weekly mean temperature and cumulative rainfall with lag times of 1-5 months using spline functions. We examined the duration of vector control and cluster management in dengue clusters > = 10 cases from 2000 to 2010 and used the information as an indicative window of the time required to mitigate an outbreak. Finally, we assessed the gap between forecast and successful control to determine the optimal timing for issuing an early warning in the study area. Our findings show that increasing weekly mean temperature and cumulative rainfall precede risks of increasing dengue cases by 4-20 and 8-20 weeks, respectively. These lag times provided a forecast window of 1-5 months based on the observed weather data. Based on previous vector control operations, the time needed to curb dengue outbreaks ranged from 1-3 months with a median duration of 2 months. Thus, a dengue early warning forecast given 3 months ahead of the onset of a probable epidemic would give local authorities sufficient time to mitigate an outbreak. CONCLUSIONS: Optimal timing of a dengue forecast increases the functional value of an early warning system and enhances cost-effectiveness of vector control operations in response to forecasted risks. We emphasize the importance of considering the forecast-mitigation gaps in respective study areas when developing a dengue forecasting model.

  10. Pichia pastoris-expressed Dengue 3 Envelope-based Virus-like Particles Elicit Predominantly Domain III-Focused High Titer Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Lav eTripathi

    2015-09-01

    Full Text Available Dengue poses a serious public health risk to nearly half the global population. It causes ~400 million infections annually and is considered to be one of the fastest spreading vector-borne diseases. Four distinct serotypes of dengue viruses (DENV-1, -2, -3 and -4 cause dengue disease, which may be either mild or extremely severe. Antibody-dependent enhancement (ADE, by pre-existing cross-reactive antibodies, is considered to be the major mechanism underlying severe disease. This mandates that a preventive vaccine must confer simultaneous and durable immunity to each of the four prevalent DENV serotypes. Recently, we used Pichia pastoris, to express recombinant DENV-2 E ectodomain, and found that it assembled into virus-like particles (VLPs, in the absence of prM, implicated in the elicitation of ADE-mediating antibodies. These VLPs elicited predominantly type-specific neutralizing antibodies that conferred significant protection against lethal DENV-2 challenge, in a mouse model. The current work is an extension of this approach to develop prM-lacking DENV-3 E VLPs. Our data reveal that P. pastoris-produced DENV-3 E VLPs not only preserve the antigenic integrity of the major neutralizing epitopes, but also elicit potent DENV-3 virus-neutralizing antibodies. Further, these neutralizing antibodies appear to be exclusively directed towards domain III of the DENV-3 E VLPs. Significantly, they also lack discernible ADE potential towards heterotypic DENVs. Taken together with the high productivity of the P. pastoris expression system, this approach could potentially pave the way towards developing a DENV E-based, inexpensive, safe and efficacious tetravalent sub-unit vaccine, for use in resource-poor dengue endemic countries.

  11. B cells contribute to MS pathogenesis through antibody-dependent and antibody-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Wilson HL

    2012-05-01

    Full Text Available Heather L Wilson1,21Vaccine and Infectious Disease Organization-International Vaccine Center, 2Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: For many years, central dogma defined multiple sclerosis (MS as a T cell-driven autoimmune disorder; however, over the past decade there has been a burgeoning recognition that B cells contribute to the pathogenesis of certain MS disease subtypes. B cells may contribute to MS pathogenesis through production of autoantibodies (or antibodies directed at foreign bodies, which unfortunately cross-react with self-antigens, through promotion of T cell activation via antigen presentation, or through production of cytokines. This review highlights evidence for antibody-dependent and antibody-independent B cell involvement in MS pathogenesis.Keywords: autoantibodies, antibody targets, clinically isolated MS, primary progressive MS, secondary progressive MS, relapsing and remitting MS, T cells, T regulatory cells

  12. X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Evans, M K; Sauer, S J; Nath, S; Robinson, T J; Morse, M A; Devi, G R

    2016-01-01

    Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy. PMID:26821068

  13. Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

    Science.gov (United States)

    Suzuki, Mami; Yamanoi, Ayaka; Machino, Yusuke; Ootsubo, Michiko; Izawa, Ken-ichi; Kohroki, Junya; Masuho, Yasuhiko

    2016-01-01

    The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes. PMID:26254483

  14. Dengue: Challenges for Policy Makers and Vaccine Developers

    OpenAIRE

    Wilder-Smith, Annelies; Macary, Paul

    2014-01-01

    Because of the increasing incidence, geographic expansion and economic burden of dengue transmission, dengue poses major challenges to policy makers. A vaccine against dengue is urgently needed, but vaccine development has been hampered by the lack of an appropriate animal model, poor understanding of correlates of successful human immunity, the fear of immune enhancement, and viral interference in tetravalent combinations. The most suitable target epitopes for vaccines, as well as the role o...

  15. Dengue encephalitis-A rare manifestation of dengue fever

    OpenAIRE

    Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nityananda; Laxman, Mridula; Mahalingam, Soundarya

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with...

  16. Dengue Fever/Dengue Haemorrhagic Fever : Case Management

    OpenAIRE

    Nimmannitya, Suchitra

    1995-01-01

    Dengue infections caused by the four antigenically distinct dengue virus serotypes (dengue virus 1, dengue virus 2, dengue virus 3, dengue virus 4) of the family Flavivindae, are the most important arbovirus disease in man, both in terms of morbidity and mortality. The infection is transmitted from man to man by Aedes mosquitoes. Since 1956, dengue virus infection has resulted in more than 3 million hospital admissions and more than 50,000 deaths in Southeast Asia, Western Pacific countries, ...

  17. The relationship of interacting immunological components in dengue pathogenesis

    Directory of Open Access Journals (Sweden)

    Nielsen David G

    2009-11-01

    Full Text Available Abstract The World Health Organization (WHO estimates that there are over 50 million cases of dengue fever reported annually and approximately 2.5 billion people are at risk. Mild dengue fever presents with headache, fever, rash, myalgia, osteogenic pain, and lethargy. Severe disease can manifest as dengue shock syndrome (DSS or dengue hemorrhagic fever (DHF. Symptoms of DSS/DHF are leukopenia, low blood volume and pressure encephalitis, cold and sweaty skin, gastrointestinal bleeding, and spontaneous bleeding from gums and nose. Currently, there are no therapeutics available beyond supportive care and untreated complicated dengue fever can have a 50% mortality rate. According to WHO DSS/DHF is the leading cause of childhood mortality in some Asian countries. Dendritic cells are professional antigen presenting cells that are primary targets in a dengue infection. Dengue binds to Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN. DC-SIGN has a high affinity for ICAM3 which is expressed in activating T-cells. Previous studies have demonstrated an altered T-cell phenotype expressed in dengue infected patients that could be potentially mediated by dengue-infected DCs. Dengue is enhanced by three interacting components of the immune system. Dengue begins by infecting dendritic cells which in immature dendritic cells is mediated by DC-SIGN. In mature dendritic cells, antibodies can enhance dengue infection via Fc receptors. Downstream of dendritic cells T-cells become activated and generate the very cytokines implicated in vascular leak and shock in addition to activating effector cells. Both the virus and the antibodies are involved in release of complement and anaphylatoxins which can cause or exacerbate DHF/DSS. These systems are inextricable and strongly associated with dengue pathogenesis.

  18. Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity [ADCC] responses.

    Science.gov (United States)

    Pollara, Justin; Bonsignori, Mattia; Moody, M Anthony; Pazgier, Marzena; Haynes, Barton F; Ferrari, Guido

    2013-07-01

    Antibody dependent cellular cytotoxicity [ADCC] has been suggested to play an important role in control of Human Immunodeficiency Virus-1 [HIV-1] viral load and protection from infection. ADCC antibody responses have been mapped to multiple linear and conformational epitopes within the HIV-1 envelope glycoproteins gp120 and gp41. Many epitopes targeted by antibodies that mediate ADCC overlap with those recognized by antibodies capable of virus neutralization. In addition, recent studies conducted with human monoclonal antibodies derived from HIV-1 infected individuals and HIV-1 vaccine-candidate vaccinees have identified a number of antibodies that lack the ability to capture primary HIV-1 isolates or mediate neutralizing activity, but are able to bind to the surface of infected CD4+ T cells and mediate ADCC. Of note, the conformational changes in the gp120 that may not exclusively relate to binding of the CD4 molecule are important in exposing epitopes recognized by ADCC responses. Here we discuss the HIV-1 envelope epitopes targeted by ADCC antibodies in the context of the potential protective capacities of ADCC. PMID:24191939

  19. The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral replication in normal out-bred mice resulting in lethal multi-organ disease.

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    Andrew K I Falconar

    Full Text Available Antibody-enhanced replication (AER of dengue type-2 virus (DENV-2 strains and production of antibody-enhanced disease (AED was tested in out-bred mice. Polyclonal antibodies (PAbs generated against the nonstructural-1 (NS1 glycoprotein candidate vaccine of the New Guinea-C (NG-C or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD₅₀ of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS, displayed by diffuse alveolar damage (DAD resulting from i dramatic interstitial alveolar septa-thickening with mononuclear cells, ii some hyperplasia of alveolar type-II pneumocytes, iii copious intra-alveolar protein secretion, iv some hyaline membrane-covered alveolar walls, and v DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human "severe dengue" cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines

  20. Dengue and dengue haemorrhagic fever: Indian perspective

    Indian Academy of Sciences (India)

    U C Chaturvedi; Rachna Nagar

    2008-11-01

    The relationship of this country with dengue has been long and intense. The first recorded epidemic of clinically dengue-like illness occurred at Madras in 1780 and the dengue virus was isolated for the first time almost simultaneously in Japan and Calcutta in 1943–1944. After the first virologically proved epidemic of dengue fever along the East Coast of India in 1963–1964, it spread to allover the country. The first full-blown epidemic of the severe form of the illness, the dengue haemorrhagic fever/dengue shock syndrome occurred in North India in 1996. Aedes aegypti is the vector for transmission of the disease. Vaccines or antiviral drugs are not available for dengue viruses; the only effective way to prevent epidemic degure fever/dengue haemorrhagic fever (DF/DHF) is to control the mosquito vector, Aedes aegypti and prevent its bite. This country has few virus laboratories and some of them have done excellent work in the area of molecular epidemiology, immunopathology and vaccine development. Selected work done in this country on the problems of dengue is presented here.

  1. Dengue fever (image)

    Science.gov (United States)

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  2. Mania in dengue fever

    OpenAIRE

    Anurag Jhanjee; Bhatia, M.S.; Shruti Srivastava

    2011-01-01

    Dengue fever, also known as break bone fever, is a mosquito-borne infection that causes a severe flu-like illness. During the last few years, there had been increasing reports of dengue fever with unusual manifestations, primarily with neurological symptoms. Psychiatric morbidity during acute dengue infection has rarely been reported. There has not been any systemic study mentioning the prevalence and pattern of psychiatric sequelae. We report a 28-year-old male who after an acute dengue infe...

  3. Hypokalemic quadriparesis in dengue

    OpenAIRE

    Mishra, Vikas; Harbada, Rishit; Sharma, Akhilesh; Mishra, Meenakshi

    2015-01-01

    Dengue infection is the leading cause of illness and death in tropical and subtropical regions of the world. The common complications associated with dengue fever are usual hematological abnormalities, shock, and organ failure. The neurological complications of dengue are uncommon. However, evidence of dengue virus neurotropism and complications has been slowly but surely rising as seen from increased literature on this subject over the last decade. We report an uncommon case of hypokalemic q...

  4. Post-dengue parkinsonism

    OpenAIRE

    Azmin, Shahrul; SAHATHEVAN, Ramesh; Suehazlyn, Zainudin; Law, Zhe Kang; Rabani, Remli; Nafisah, Wan Yahya; Tan, Hui Jan; NORLINAH, Mohamed Ibrahim

    2013-01-01

    Background Dengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature. Case presentation A previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations. Conclusions The authors...

  5. Post dengue neurological complication

    OpenAIRE

    Hasliza, AH; Tohid, H; Loh, KY; Santhi, P

    2015-01-01

    Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain–Barre syndrome (GBS) is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE) followed by an upper respirator...

  6. How antibodies alter the cell entry pathway of dengue virus particles in macrophages

    Science.gov (United States)

    Ayala-Nunez, Nilda V.; Hoornweg, Tabitha E.; van de Pol, Denise P.I.; Sjollema, Klaas A.; Flipse, Jacky; van der Schaar, Hilde M.; Smit, Jolanda M.

    2016-01-01

    Antibody-dependent enhancement of dengue virus (DENV) infection plays an important role in the exacerbation of DENV-induced disease. To understand how antibodies influence the fate of DENV particles, we explored the cell entry pathway of DENV in the absence and presence of antibodies in macrophage-like P388D1 cells. Recent studies unraveled that both mature and immature DENV particles contribute to ADE, hence, both particles were studied. We observed that antibody-opsonized DENV enters P388D1 cells through a different pathway than non-opsonized DENV. Antibody-mediated DENV entry was dependent on FcγRs, pH, Eps15, dynamin, actin, PI3K, Rab5, and Rab7. In the absence of antibodies, DENV cell entry was FcγR, PI3K, and Rab5-independent. Live-cell imaging of fluorescently-labeled particles revealed that actin-mediated membrane protrusions facilitate virus uptake. In fact, actin protrusions were found to actively search and capture antibody-bound virus particles distantly located from the cell body, a phenomenon that is not observed in the absence of antibodies. Overall, similar results were seen for antibody-opsonized standard and antibody-bound immature DENV preparations, indicating that the maturation status of the virus does not control the entry pathway. Collectively, our findings suggest that antibodies alter the cell entry pathway of DENV and trigger a novel mechanism of initial virus-cell contact. PMID:27385443

  7. Multi-Strain Deterministic Chaos in Dengue Epidemiology, A Challenge for Computational Mathematics

    Science.gov (United States)

    Aguiar, Maíra; Kooi, Bob W.; Stollenwerk, Nico

    2009-09-01

    Recently, we have analysed epidemiological models of competing strains of pathogens and hence differences in transmission for first versus secondary infection due to interaction of the strains with previously aquired immunities, as has been described for dengue fever, known as antibody dependent enhancement (ADE). These models show a rich variety of dynamics through bifurcations up to deterministic chaos. Including temporary cross-immunity even enlarges the parameter range of such chaotic attractors, and also gives rise to various coexisting attractors, which are difficult to identify by standard numerical bifurcation programs using continuation methods. A combination of techniques, including classical bifurcation plots and Lyapunov exponent spectra has to be applied in comparison to get further insight into such dynamical structures. Especially, Lyapunov spectra, which quantify the predictability horizon in the epidemiological system, are computationally very demanding. We show ways to speed up computations of such Lyapunov spectra by a factor of more than ten by parallelizing previously used sequential C programs. Such fast computations of Lyapunov spectra will be especially of use in future investigations of seasonally forced versions of the present models, as they are needed for data analysis.

  8. Selection and Characterization of DNA Aptamers Targeting All Four Serotypes of Dengue Viruses.

    Science.gov (United States)

    Chen, Heng-Li; Hsiao, Wen-Hsin; Lee, Hsiang-Chi; Wu, Suh-Chin; Cheng, Jya-Wei

    2015-01-01

    Dengue viruses (DENVs) are members of Flaviviridae family, which are associated with human disease. The envelope (E) protein plays an important role in viral infection. However, there is no effective antibody for clinical treatment due to antibody dependent enhancement of infection. In this study, using Systematic Evolution of Ligands by Exponential Enrichment (SELEX), we demonstrated the first aptamer (S15) that can bind to DENV-2 envelop protein domain III (ED3) with a high binding affinity. S15 was found to form a parallel quadruplex based on Quadfinder prediction, gel mobility assay and circular dichroism studies. Both the quadruplex structure and the sequence on 5'-end were necessary for the binding activity of S15. NMR titration experiments indicated that S15 bound to a highly conserved loop between βA and βB strands of ED3. Moreover, S15 can neutralize the infections by all four serotypes of DENVs. Our result provides a new opportunity in the development of DNA aptamers against DENVs in the future.

  9. Selection and Characterization of DNA Aptamers Targeting All Four Serotypes of Dengue Viruses.

    Directory of Open Access Journals (Sweden)

    Heng-Li Chen

    Full Text Available Dengue viruses (DENVs are members of Flaviviridae family, which are associated with human disease. The envelope (E protein plays an important role in viral infection. However, there is no effective antibody for clinical treatment due to antibody dependent enhancement of infection. In this study, using Systematic Evolution of Ligands by Exponential Enrichment (SELEX, we demonstrated the first aptamer (S15 that can bind to DENV-2 envelop protein domain III (ED3 with a high binding affinity. S15 was found to form a parallel quadruplex based on Quadfinder prediction, gel mobility assay and circular dichroism studies. Both the quadruplex structure and the sequence on 5'-end were necessary for the binding activity of S15. NMR titration experiments indicated that S15 bound to a highly conserved loop between βA and βB strands of ED3. Moreover, S15 can neutralize the infections by all four serotypes of DENVs. Our result provides a new opportunity in the development of DNA aptamers against DENVs in the future.

  10. Dengue in children

    NARCIS (Netherlands)

    Verhagen, L.M.; Groot, R. de

    2014-01-01

    Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with

  11. Autoimmune features caused by dengue fever: a case report

    OpenAIRE

    Denis Leonardo Fontes Jardim; Daniela Miti Lemos Tsukumo; Angerami, Rodrigo N.; Marco Antonio de Carvalho Filho; Mário José Abdalla Saad

    2012-01-01

    Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 leve...

  12. Research on Climate and Dengue in Malaysia: A Systematic Review

    OpenAIRE

    Hii, Yien Ling; Zaki, Rafdzah Ahmad; Aghamohammadi, Nasrin; Rocklöv, Joacim

    2016-01-01

    Background & Objectives Dengue is a climate-sensitive infectious disease. Climate-based dengue early warning may be a simple, low-cost, and effective tool for enhancing surveillance and control. Scientific studies on climate and dengue in local context form the basis for advancing the development of a climate-based early warning system. This study aims to review the current status of scientific studies in climate and dengue and the prospect or challenges of such research on a climate-based de...

  13. Antibody-dependent NK cell activation is associated with late kidney allograft dysfunction and the complement-independent alloreactive potential of donor-specific antibodies

    Directory of Open Access Journals (Sweden)

    Tristan Legris

    2016-08-01

    Full Text Available Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs. The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK cells as innate immune effectors of antibody-dependent cellular cytotoxicity, but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years. Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate (eGFR over a 1-year period (hazard ratio: 2.83. In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration

  14. Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor-Specific Antibodies.

    Science.gov (United States)

    Legris, Tristan; Picard, Christophe; Todorova, Dilyana; Lyonnet, Luc; Laporte, Cathy; Dumoulin, Chloé; Nicolino-Brunet, Corinne; Daniel, Laurent; Loundou, Anderson; Morange, Sophie; Bataille, Stanislas; Vacher-Coponat, Henri; Moal, Valérie; Berland, Yvon; Dignat-George, Francoise; Burtey, Stéphane; Paul, Pascale

    2016-01-01

    Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of

  15. Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer.

    Science.gov (United States)

    Kono, Koji; Takahashi, Akihiro; Ichihara, Fumiko; Sugai, Hidemitsu; Fujii, Hideki; Matsumoto, Yoshirou

    2002-10-15

    The humanized monoclonal antibody Herceptin, which specifically targets HER-2/neu, exhibits growth inhibitory activity against HER-2/neu-overexpressing tumors and is approved for therapeutic use with proved survival benefit in patients with HER-2/neu-positive breast cancer. In the present study, we investigated whether Herceptin could affect the HER-2/neu-overexpressing gastric cancer cells based on antibody-dependent cell-mediated cytotoxicity (ADCC) and compared immune effector cells from gastric cancer patients with normal individuals on ADCC. HER-2/neu-expressing gastric cancer cells could be killed by Herceptin-mediated ADCC and the Herceptin-induced ADCC correlated with the degree of HER-2/neu expression on the gastric cancer cells. However, the Herceptin-mediated ADCC was significantly impaired in peripheral blood mononuclear cells from advanced disease patients (n = 10) compared with that in early disease (n = 12; P = 0.04) or healthy individuals (n = 10, P = 0.02). Moreover, natural killer (NK) cells purified from patients with advanced disease indicated less Herceptin-mediated ADCC in comparison with that from healthy donors (P = 0.04), whereas monocytes purified from the patients showed an almost equal amount of Herceptin-mediated ADCC in comparison with that from healthy individuals, indicating that NK cell dysfunction contributed to the impaired Herceptin-mediated ADCC in gastric cancer patients. Furthermore, the NK-cell dysfunction on Herceptin-mediated ADCC correlated with the down-regulation of CD16zeta expression in the patients, and interleukin 2 ex vivo treatment of NK cells could restore the impairment of Herceptin-mediated ADCC, concomitant to the normalization of the expression of CD16zeta molecules. Thus, some modalities such as interleukin 2 treatment aimed at reversing NK dysfunction may be necessary for successful Herceptin treatment of gastric cancer. PMID:12384543

  16. Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes.

    Science.gov (United States)

    Cheng, Yi-Lin; Lin, Yee-Shin; Chen, Chia-Ling; Tsai, Tsung-Ting; Tsai, Cheng-Chieh; Wu, Yan-Wei; Ou, Yi-Dan; Chu, Yu-Yi; Wang, Ju-Ming; Yu, Chia-Yi; Lin, Chiou-Feng

    2016-01-01

    Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A. PMID:27561946

  17. Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes

    Science.gov (United States)

    Cheng, Yi-Lin; Lin, Yee-Shin; Chen, Chia-Ling; Tsai, Tsung-Ting; Tsai, Cheng-Chieh; Wu, Yan-Wei; Ou, Yi-Dan; Chu, Yu-Yi; Wang, Ju-Ming; Yu, Chia-Yi; Lin, Chiou-Feng

    2016-01-01

    Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A. PMID:27561946

  18. Dengue Virus Infection in Africa

    OpenAIRE

    Amarasinghe, Ananda; Kuritsky, Joel N.; Letson, G. William; Margolis, Harold S

    2011-01-01

    Reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in Africa. During 1960–2010, a total of 22 countries in Africa reported sporadic cases or outbreaks of dengue; 12 other countries in Africa reported dengue only in travelers. The presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virus infection in all or many parts of Africa. Dengue is likely underrecognized and u...

  19. Dengue-associated neuromuscular complications

    OpenAIRE

    Ravindra Kumar Garg; Hardeep Singh Malhotra; Amita Jain; Kiran Preet Malhotra

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evo...

  20. Acute pancreatitis complicating severe dengue

    OpenAIRE

    Vishakha Jain; O P Gupta; Tarun Rao; Siddharth Rao

    2014-01-01

    Dengue is an arthropod borne viral infection endemic in tropical and subtropical continent. Severe dengue is life threatening. Various atypical presentations of dengue have been documented. But we present a rare and fatal complication of severe dengue in form of acute pancreatitis. A 27-year-old male had presented with severe dengue in decompensated shock and with pain in abdomen due to pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly understood, but various mecha...

  1. Dengue encephalitis-A rare manifestation of dengue fever

    Institute of Scientific and Technical Information of China (English)

    Deepak Madi; Basavaprabhu Achappa; John T Ramapuram; Nityananda Chowta; Mridula Laxman; Soundarya Mahalingam

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with fever, altered sensorium and seizures. Dengue NS-1 antigen test was reactive. Dengue IgM was also positive. CSF PCR was negative for herpes simplex 1 & 2. Dengue encephalitis should be considered in the differential diagnosis of fever with altered sensorium, especially in countries like India where dengue is rampant.

  2. Relative contribution of dengue prM- and E-specific polyclonal antibodies to neutralization and enhancement.

    Science.gov (United States)

    Rodpothong, P; Boonarkart, Ch; Ruangrung, K; Onsirisakul, N; Kanistanon, D; Auewarakul, P

    2016-01-01

    Viral surface proteins, premembrane protein (prM) and envelope (E) protein have been shown to induce a production of antibodies that are involved in both enhancement and neutralization. To explore the feasibility of modifying the relative immune responses to prM and E proteins, four DNA constructs were created and administered into groups of Balb/c mice; pPW01 contains prM and E genes of DENV1, pPW02 contains prM and E genes of DENV2, pPW03 contains DENV1 prM and DENV2 E, and pPW04 contains DENV2 prM and DENV1 E. Exchange of either prM or E from a heterologous serotype does not appear to have an effect on the immunogenicity of the proteins. We have proved that the chimeric pPW03 and pPW04 constructs can produce humoral response in mice. Immunized sera were subjected to neutralization and enhancement assays against DENV2. The results showed that only serotype-specific anti-E antibodies conferred protective function, while the cross-reactive anti-E and anti-prM enhanced infection. In addition, the enhancement of DENV2 infection exhibited a serotype-preference for anti-E antibodies while such response was not observed with anti-prM, reflecting a degree of structural conservation of prM. Taken together, neutralization and enhancement appeared to occur at the same time during the course of infection. Successful prevention of severe symptoms of DENV infection depends on the ability to induce high levels of neutralizing antibodies to subdue the effect of enhancing antibodies. PMID:27640435

  3. First Outbreak of Dengue Hemorrhagic Fever, Bangladesh

    OpenAIRE

    Rahman, Mahbubur; Rahman, Khalilur; Siddque, A. K.; Shoma, Shereen; A. H. M. Kamal; Ali, K.S.; Nisaluk, Ananda; Breiman, Robert F.

    2002-01-01

    During the first countrywide outbreak of dengue hemorrhagic fever in Bangladesh, we conducted surveillance for dengue at a hospital in Dhaka. Of 176 patients, primarily adults, found positive for dengue, 60.2% had dengue fever, 39.2% dengue hemorrhagic fever, and 0.6% dengue shock syndrome. The Dengue virus 3 serotype was detected in eight patients.

  4. Exploring the relationships between dengue fever knowledge and Aedes aegypti breeding in St Catherine Parish, Jamaica: a pilot of enhanced low-cost surveillance

    Directory of Open Access Journals (Sweden)

    Stoler J

    2011-06-01

    Full Text Available Justin Stoler1, Stephanie K Brodine2, Simeon Bromfield3, John R Weeks1, Henroy P Scarlett41Department of Geography, San Diego State University, San Diego, CA, USA; 2Graduate School of Public Health, San Diego State University, San Diego, CA, USA; 3Mosquito Control Section, St Catherine Health Department, Spanish Town, Jamaica; 4Department of Community Health and Psychiatry, University of the West Indies at Mona, Kingston, JamaicaPurpose: Dengue fever has re-emerged as an increasingly significant global health threat amid diminishing resources pledged for its control in developing nations. Efforts to limit breeding of the dengue vector Aedes aegypti are often hampered by lack of community awareness of the disease.Methods: Sixty-eight households in St Catherine Parish, Jamaica completed a pilot knowledge, attitude, and practice questionnaire as part of a routine container survey for presence of A. aegypti larvae.Results: Infestation levels were high according to traditional Stegomyia indices (Breteau index = 325; however, general knowledge of dengue symptoms, A. aegypti breeding sites, and preventive practices was low. After examining the links between demographic characteristics, dengue knowledge, and the number of breeding sites per house, higher educational achievement was associated with higher dengue knowledge, but also with more unprotected containers. Overall dengue knowledge was not associated with household container counts. Spatial statistics identified weak clustering of larvae-positive containers, and larvae were concentrated in three key container types.Conclusion: Residents may only understand the role of certain container types, and significant gaps in general knowledge of the disease may inhibit vector control. This pilot demonstrates the feasibility of conducting inexpensive, rapid assessment of community knowledge and breeding levels for local governments lacking the resources for a more methodologically robust vector assessment

  5. Dengue disease in Malaysia

    OpenAIRE

    Cheong, Yoon Ling

    2015-01-01

    Der Klimawandel hat weitreichende Folgen auf die Gesundheit der Menschen. Insbesondere Übertragungskrankheiten wie Dengue bekommen global gesehen eine zunehmende Bedeutung. Über die raumzeitliche Verteilung und das Umwelt-Dengue Risiko ist bisher wenig bekannt. Das Hauptziel dieser Dissertation war es daher, die Ätiologie von Dengue in einem hoch endemischen Gebiet besser zu verstehen. Es wurden räumliche Muster des Krankheitsauftretens untersucht, die anschließend in einer Umwelt-Risiko Anal...

  6. Dengue: uma nova abordagem Dengue: a reappraisal

    Directory of Open Access Journals (Sweden)

    José Carlos Serufo

    2000-10-01

    Full Text Available Os conceitos de dengue clássico, com ou sem hemorragia, e de febre hemorrágica do dengue (FHD que, pode cursar sem fenômenos hemorrágicos, com ou sem síndrome do choque do dengue (SCD, são revistos neste artigo. As definições clássicas propostas, úteis em outros tempos, geram confusão e dificultam a tomada de decisões no momento do tratamento dos pacientes com as formas graves da doença porque deixaram de incorporar novos conceitos e avanços terapêuticos. A classificação do dengue proposta neste trabalho, e apresentada em fluxograma, incorpora os conceitos atuais de sepse, síndrome da resposta inflamatória sistêmica (SIRS e síndrome da angústia respiratória do adulto (SARA. A nova classificação serve de guia para orientar a conduta terapêutica inicial e aproxima o tratamento do dengue aos protocolos e rotinas já implantados nos diversos centros hospitalares de urgência, facilitando a atuação dos serviços de saúde em situações de surtos epidêmicos.Previous definition of classic dengue, with or without bleeding, and of dengue hemorrhagic fever (DHF that may evolve without bleeding and with or without dengue shock syndrome (DSS are reviewed here. The classical approach to the diagnosis and treatment of dengue, although useful in the past, nowadays breeds confusion and adds a burden to the physician's task of decision-making regarding the treatment of patients with severe forms of the disease. The classification of dengue proposed in this paper, and summarized in a diagram, incorporates new concepts about sepsis, systemic inflammatory response syndrome (SIRS, and acute respiratory distress syndrome (ARDS. This new approach, in our view, is a useful guide to initial evaluation and treatment of the disease. It also approximates the dengue syndrome to other protocols and medical procedures routinely used in intensive care units, making it easier to be followed by the health personnel working in areas subject to

  7. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Directory of Open Access Journals (Sweden)

    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  8. Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity

    OpenAIRE

    Konno, Yoshinobu; Kobayashi, Yuki; Takahashi, Ken; TAKAHASHI, Eiji; Sakae, Shinji; Wakitani, Masako; Yamano, Kazuya; Suzawa, Toshiyuki; Yano, Keiichi; Ohta, Toshio; Koike, Masamichi; Wakamatsu, Kaori; Hosoi, Shinji

    2011-01-01

    Antibody-dependent cellular cytotoxicity (ADCC) is dependent on the fucose content of oligosaccharides bound to monoclonal antibodies (MAbs). As MAbs with a low fucose content exhibit high ADCC activity, it is important to control the defucosylation levels (deFuc%) of MAbs and to analyze the factors that affect deFuc%. In this study, we observed that the deFuc% was inversely related to culture medium osmolality for MAbs produced in the rat hybridoma cell line YB2/0, with r2 values as high as ...

  9. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  10. Post dengue neurological complication.

    Science.gov (United States)

    Hasliza, A H; Tohid, H; Loh, K Y; Santhi, P

    2015-01-01

    Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain-Barre syndrome (GBS) is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE) followed by an upper respiratory tract infection (URTI) weeks prior to her presentation rendering GBS secondary to the post viral URTI and AGE as the most likely diagnosis. Presence of thrombocytopenia was the only clue for dengue in this case. PMID:27099661

  11. DengueME: A Tool for the Modeling and Simulation of Dengue Spatiotemporal Dynamics †

    Science.gov (United States)

    de Lima, Tiago França Melo; Lana, Raquel Martins; de Senna Carneiro, Tiago Garcia; Codeço, Cláudia Torres; Machado, Gabriel Souza; Ferreira, Lucas Saraiva; de Castro Medeiros, Líliam César; Davis Junior, Clodoveu Augusto

    2016-01-01

    The prevention and control of dengue are great public health challenges for many countries, particularly since 2015, as other arboviruses have been observed to interact significantly with dengue virus. Different approaches and methodologies have been proposed and discussed by the research community. An important tool widely used is modeling and simulation, which help us to understand epidemic dynamics and create scenarios to support planning and decision making processes. With this aim, we proposed and developed DengueME, a collaborative open source platform to simulate dengue disease and its vector’s dynamics. It supports compartmental and individual-based models, implemented over a GIS database, that represent Aedes aegypti population dynamics, human demography, human mobility, urban landscape and dengue transmission mediated by human and mosquito encounters. A user-friendly graphical interface was developed to facilitate model configuration and data input, and a library of models was developed to support teaching-learning activities. DengueME was applied in study cases and evaluated by specialists. Other improvements will be made in future work, to enhance its extensibility and usability. PMID:27649226

  12. DengueME: A Tool for the Modeling and Simulation of Dengue Spatiotemporal Dynamics

    Directory of Open Access Journals (Sweden)

    Tiago França Melo de Lima

    2016-09-01

    Full Text Available The prevention and control of dengue are great public health challenges for many countries, particularly since 2015, as other arboviruses have been observed to interact significantly with dengue virus. Different approaches and methodologies have been proposed and discussed by the research community. An important tool widely used is modeling and simulation, which help us to understand epidemic dynamics and create scenarios to support planning and decision making processes. With this aim, we proposed and developed DengueME, a collaborative open source platform to simulate dengue disease and its vector’s dynamics. It supports compartmental and individual-based models, implemented over a GIS database, that represent Aedes aegypti population dynamics, human demography, human mobility, urban landscape and dengue transmission mediated by human and mosquito encounters. A user-friendly graphical interface was developed to facilitate model configuration and data input, and a library of models was developed to support teaching-learning activities. DengueME was applied in study cases and evaluated by specialists. Other improvements will be made in future work, to enhance its extensibility and usability.

  13. DengueME: A Tool for the Modeling and Simulation of Dengue Spatiotemporal Dynamics.

    Science.gov (United States)

    de Lima, Tiago França Melo; Lana, Raquel Martins; de Senna Carneiro, Tiago Garcia; Codeço, Cláudia Torres; Machado, Gabriel Souza; Ferreira, Lucas Saraiva; de Castro Medeiros, Líliam César; Davis Junior, Clodoveu Augusto

    2016-01-01

    The prevention and control of dengue are great public health challenges for many countries, particularly since 2015, as other arboviruses have been observed to interact significantly with dengue virus. Different approaches and methodologies have been proposed and discussed by the research community. An important tool widely used is modeling and simulation, which help us to understand epidemic dynamics and create scenarios to support planning and decision making processes. With this aim, we proposed and developed DengueME, a collaborative open source platform to simulate dengue disease and its vector's dynamics. It supports compartmental and individual-based models, implemented over a GIS database, that represent Aedes aegypti population dynamics, human demography, human mobility, urban landscape and dengue transmission mediated by human and mosquito encounters. A user-friendly graphical interface was developed to facilitate model configuration and data input, and a library of models was developed to support teaching-learning activities. DengueME was applied in study cases and evaluated by specialists. Other improvements will be made in future work, to enhance its extensibility and usability. PMID:27649226

  14. A rare case of dengue encephalitis

    OpenAIRE

    Rao, Sachin; Kumar, Manish; Ghosh, Soumik; Gadpayle, Adesh Kumar

    2013-01-01

    Dengue fever has a variable clinical spectrum ranging from asymptomatic infection to life-threatening dengue haemorrhagic fever and dengue shock syndrome. However, neurological complications, in general, are unusual. Dengue encephalopathy is not an unknown entity; however, dengue encephalitis, a direct neuronal infiltration by the dengue virus, is an extremely rare disease. Although dengue is classically considered a non-neurotropic virus, there is increasing evidence for dengue viral neurotr...

  15. Quantitative evaluation of fucose reducing effects in a humanized antibody on Fcγ receptor binding and antibody-dependent cell-mediated cytotoxicity activities.

    Science.gov (United States)

    Chung, Shan; Quarmby, Valerie; Gao, Xiaoying; Ying, Yong; Lin, Linda; Reed, Chae; Fong, Chris; Lau, Wendy; Qiu, Zhihua J; Shen, Amy; Vanderlaan, Martin; Song, An

    2012-01-01

    The presence or absence of core fucose in the Fc region N-linked glycans of antibodies affects their binding affinity toward FcγRIIIa as well as their antibody-dependent cell-mediated cytotoxicity (ADCC) activity. However, the quantitative nature of this structure-function relationship remains unclear. In this study, the in vitro biological activity of an afucosylated anti-CD20 antibody was fully characterized. Further, the effect of fucose reduction on Fc effector functions was quantitatively evaluated using the afucosylated antibody, its "regular" fucosylated counterpart and a series of mixtures containing varying proportions of "regular" and afucosylated materials. Compared with the "regular" fucosylated antibody, the afucosylated antibody demonstrated similar binding interactions with the target antigen (CD20), C1q and FcγRIa, moderate increases in binding to FcγRIIa and IIb, and substantially increased binding to FcγRIIIa. The afucosylated antibodies also showed comparable complement-dependent cytotoxicity activity but markedly increased ADCC activity. Based on EC 50 values derived from dose-response curves, our results indicate that the amount of afucosylated glycan in antibody samples correlate with both FcγRIIIa binding activity and ADCC activity in a linear fashion. Furthermore, the extent of ADCC enhancement due to fucose depletion was not affected by the FcγRIIIa genotype of the effector cells.

  16. Dengue Disease Risk Mental Models in the City of Dhaka, Bangladesh: Juxtapositions and Gaps Between the Public and Experts.

    Science.gov (United States)

    Dhar-Chowdhury, Parnali; Haque, C Emdad; Driedger, S Michelle

    2016-05-01

    Worldwide, more than 50 million cases of dengue fever are reported every year in at least 124 countries, and it is estimated that approximately 2.5 billion people are at risk for dengue infection. In Bangladesh, the recurrence of dengue has become a growing public health threat. Notably, knowledge and perceptions of dengue disease risk, particularly among the public, are not well understood. Recognizing the importance of assessing risk perception, we adopted a comparative approach to examine a generic methodology to assess diverse sets of beliefs related to dengue disease risk. Our study mapped existing knowledge structures regarding the risk associated with dengue virus, its vector (Aedes mosquitoes), water container use, and human activities in the city of Dhaka, Bangladesh. "Public mental models" were developed from interviews and focus group discussions with diverse community groups; "expert mental models" were formulated based on open-ended discussions with experts in the pertinent fields. A comparative assessment of the public's and experts' knowledge and perception of dengue disease risk has revealed significant gaps in the perception of: (a) disease risk indicators and measurements; (b) disease severity; (c) control of disease spread; and (d) the institutions responsible for intervention. This assessment further identifies misconceptions in public perception regarding: (a) causes of dengue disease; (b) dengue disease symptoms; (c) dengue disease severity; (d) dengue vector ecology; and (e) dengue disease transmission. Based on these results, recommendations are put forward for improving communication of dengue risk and practicing local community engagement and knowledge enhancement in Bangladesh. PMID:26387980

  17. Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

    Science.gov (United States)

    Lorenzi, Olga D; Gregory, Christopher J; Santiago, Luis Manuel; Acosta, Héctor; Galarza, Ivonne E; Hunsperger, Elizabeth; Muñoz, Jorge; Bui, Duy M; Oberste, M Steven; Peñaranda, Silvia; García-Gubern, Carlos; Tomashek, Kay M

    2013-03-01

    In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs. PMID:23382160

  18. Exploring the relationships between dengue fever knowledge and Aedes aegypti breeding in St Catherine Parish, Jamaica: a pilot of enhanced low-cost surveillance

    OpenAIRE

    Stoler, Justin

    2011-01-01

    Justin Stoler1, Stephanie K Brodine2, Simeon Bromfield3, John R Weeks1, Henroy P Scarlett41Department of Geography, San Diego State University, San Diego, CA, USA; 2Graduate School of Public Health, San Diego State University, San Diego, CA, USA; 3Mosquito Control Section, St Catherine Health Department, Spanish Town, Jamaica; 4Department of Community Health and Psychiatry, University of the West Indies at Mona, Kingston, JamaicaPurpose: Dengue fever has re-emerged as an increasingly signific...

  19. Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark

    DEFF Research Database (Denmark)

    Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo;

    2016-01-01

    The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated...... epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular...... cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory...

  20. Forecast of dengue incidence using temperature and rainfall.

    Directory of Open Access Journals (Sweden)

    Yien Ling Hii

    Full Text Available INTRODUCTION: An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98% in 2004-2010 and 98% (CI = 95%-100% in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm. SIGNIFICANCE: We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization

  1. Anti-HIV-1 antibody-dependent cellular cytotoxicity mediated by hyperimmune bovine colostrum IgG.

    Science.gov (United States)

    Kramski, Marit; Lichtfuss, Gregor F; Navis, Marjon; Isitman, Gamze; Wren, Leia; Rawlin, Grant; Center, Rob J; Jaworowski, Anthony; Kent, Stephen J; Purcell, Damian F J

    2012-10-01

    Antibodies with antibody-dependent cellular cytotoxicity (ADCC) activity play an important role in protection against HIV-1 infection, but generating sufficient amounts of antibodies to study their protective efficacy is difficult. HIV-specific IgG can be easily and inexpensively produced in large quantities using bovine colostrum. We previously vaccinated cows with HIV-1 envelope gp140 and elicited high titers of anti-gp140-binding IgG in colostrum. In the present study, we determined whether bovine antibodies would also demonstrate specific cytotoxic activity. We found that bovine IgG bind to Fcγ-receptors (FcγRs) on human neutrophils, monocytes, and NK cells in a dose-dependent manner. Antibody-dependent killing was observed in the presence of anti-HIV-1 colostrum IgG but not nonimmune colostrum IgG. Killing was dependent on Fc and FcγR interaction since ADDC activity was not seen with F(ab')(2) fragments. ADCC activity was primarily mediated by CD14(+) monocytes with FcγRIIa (CD32a) as the major receptor responsible for monocyte-mediated ADCC in response to bovine IgG. In conclusion, we demonstrate that bovine anti-HIV colostrum IgG have robust HIV-1-specific ADCC activity and therefore offer a useful source of antibodies able to provide a rapid and potent response against HIV-1 infection. This could assist the development of novel Ab-mediated approaches for prevention of HIV-1 transmission. PMID:22730083

  2. Dengue fever: atypical manifestation

    Directory of Open Access Journals (Sweden)

    Nataraj Gangasiddaiah

    2014-08-01

    Full Text Available Dengue fever is affecting millions of population globally. For the past one decade, we have seen several outbreaks and even causing significant mortality of affected population. We witnessed numerous pattern and multisystem presentation of dengue in this period. The CNS manifestation like encephalitis, polyneuropathy (GB like syndrome and paresthesias were uncommonly reported priorly. Pancreatitis, polyserositis, carditis of varying severity and hepatic failure are the, some of atypical manifestations observed in recent out breaks. So dengue illness can presents with multi system involvement and can account to significant mortality. Here an attempt was done to present varying, uncommon and atypical manifestation of dengue illness. [Int J Res Med Sci 2014; 2(4.000: 1804-1806

  3. Dengue epidemiology in Thanjavur and Trichy district, Tamilnadu - Jan 2011-Dec 2011

    OpenAIRE

    Chinnathambi Kalidoss Bhuvaneswari; Ramalingam Senthil Raja; Kavita Arunagiri; Shambasivam Mohana; Karuppanan Sathiyamurthy; Kaveri Krishnasamy; Palani Gunasekaran

    2011-01-01

    Background: Dengue infection is emerging as a serious public health problem in Tamil Nadu. An enhanced surveillance system can generate information on the epidemiology of the disease, which is essential for planning and development of relevant control/preventive measures against Dengue. Materials and Methods: A prospective descriptive study was undertaken between January 2011 to December 2011, by testing suspected Dengue patients attending Thanjavur Medical College and Trichy Hospital (TMCH, ...

  4. The dengue viruses.

    OpenAIRE

    Henchal, E A; Putnak, J R

    1990-01-01

    Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the...

  5. Dengue disease outbreak detection.

    Science.gov (United States)

    Dayama, Pankaj; Sampath, Kameshwaran

    2014-01-01

    Early detection of outbreak of a disease may help in timely and effective public health interventions. Our motivation for this work is to assist EHD planning officer to analyze the incidence data and based on it declare whether there is an outbreak or not. In this paper, we develop ensemble of multiple techniques for detecting dengue disease outbreak. These techniques are applied to dengue incidence data from Singapore and results are summarized.

  6. Treatment of dengue fever

    OpenAIRE

    Rajapakse, Senaka

    2012-01-01

    Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decad...

  7. Cells of the J774 macrophage cell line are primed for antibody-dependent cell-mediated cytotoxicity following exposure to γ-irradiation

    International Nuclear Information System (INIS)

    Activation of macrophages (M phi) for host defense against tumor cells follows a sequence of priming events followed by an initiating stimulus that results in production and release of cytotoxic molecules that mediate target cell killing. The authors have developed a model to study specific macrophage cytotoxicity in vitro utilizing a cultured murine M phi cell line, J774. Specific cytotoxicity of cultured human gastrointestinal tumor cells is achieved in the presence of murine IgG2a monoclonal antibody (mAb) 17-1-A. The ability of these cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) is greatly enhanced following gamma-irradiation. ADCC can be demonstrated at mAb 17-1-A concentrations greater than or equal to 1 microgram/ml and effector/target cell ratios greater than or equal to 2. Exposure to doses greater than or equal to 10 Gy of gamma-irradiation increases ADCC threefold. Varying the duration from J774 M phi exposure to γ-irradiation until addition of antibody-coated target cells showed that the primed state for ADCC is stable for at least 8 days but approximately 24 hr is required for complete development of the primed state. mAb-dependent target cell death begins 8 hr after addition of mAb and labeled target cells to primed effector cells and is complete by 24 hr. Incubation of unirradiated J774 M phi effector cells with recombinant murine interferon-γ (rmIFN-γ) also results in enhanced ADCC, but the extent of target cell killing achieved is less than that following priming by γ-irradiation. Concomitant priming of γ-irradiated J774 M phi with rmIFN-γ increases the extent of ADCC. Further study of irradiated J774 cells may elucidate the molecular pathways utilized by M phi for achieving and maintaining the primed state for ADCC

  8. Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever

    OpenAIRE

    Javier Mota; Rebeca Rico-Hesse

    2011-01-01

    Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infec...

  9. Treatment of dengue fever

    Directory of Open Access Journals (Sweden)

    Rajapakse S

    2012-07-01

    Full Text Available Senaka Rajapakse,1,2 Chaturaka Rodrigo,1 Anoja Rajapakse31Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka; 2Lincoln County Hospital, United Lincolnshire NHS Trust, Lincoln, UK; 3Kings Mill Hospital, Sherwood Forest NHS Foundation Trust, Mansfield, UKAbstract: The endemic area for dengue fever extends over 60 countries, and approximately 2.5 billion people are at risk of infection. The incidence of dengue has multiplied many times over the last five decades at an alarming rate. In the endemic areas, waves of infection occur in epidemics, with thousands of individuals affected, creating a huge burden on the limited resources of a country's health care system. While the illness passes off as a simple febrile episode in many, a few have a severe illness marked by hypovolemic shock and bleeding. Iatrogenic fluid overload in the management may further complicate the picture. In this severe form dengue can be fatal. Tackling the burden of dengue is impeded by several issues, including a lack of understanding about the exact pathophysiology of the infection, inability to successfully control the vector population, lack of specific therapy against the virus, and the technical difficulties in developing a vaccine. This review provides an overview on the epidemiology, natural history, management strategies, and future directions for research on dengue, including the potential for development of a vaccine.Keywords: dengue, treatment, fluid resuscitation

  10. Detection of dengue virus in platelets isolated from dengue patients.

    Science.gov (United States)

    Noisakran, Sansanee; Gibbons, Robert V; Songprakhon, Pucharee; Jairungsri, Aroonroong; Ajariyakhajorn, Chuanpis; Nisalak, Ananda; Jarman, Richard G; Malasit, Prida; Chokephaibulkit, Kulkanya; Perng, Guey Chuen

    2009-03-01

    Though thrombocytopenia or dysfunction of platelets is common in dengue virus infection, the role of platelets has not been established. We enrolled 33 hospitalized children with serologically confirmed dengue virus infection. Blood specimens were collected during hospitalization. Platelets and plasma were isolated from the whole blood. Detection of dengue virus in plasma and platelets was carried out by RT-PCR with primers that can differentiate different dengue serotypes simultaneously, and by electron transmission microscopy (EM). Dengue viral RNA was detected in the platelets and plasma by conventional RT-PCR. A significantly higher percentage of dengue viral RNA was detected in platelets than in plasma (p = 0.03). Platelets isolated 5 days after onset of fever were most likely positive for viral RNA. Concurrent infection or co-circulation with multiple dengue serotypes was observed in 12% of patients. Infrequently, negative-stranded dengue viral RNA was detected in platelets and in plasma. Importantly, EM confirmed the presence of dengue viral-like particles inside platelets prepared from dengue patients. Our findings suggest the presence of dengue virus in platelets may be associated with the dysfunction of platelets observed in dengue patients.

  11. Antibody with an engineered Fc region as a therapeutic agent against dengue virus infection.

    Science.gov (United States)

    Ramadhany, Ririn; Hirai, Itaru; Sasaki, Tadahiro; Ono, Ken-ichiro; Ramasoota, Pongrama; Ikuta, Kazuyoshi; Kurosu, Takeshi

    2015-12-01

    Antibody-dependent enhancement (ADE) of dengue virus (DENV) infectivity is thought to play a crucial role in severe dengue disease. It occurs when pre-existing sub-neutralizing anti-DENV antibody (Ab) produced from a primary infection encounters a DENV serotype different from that of the initial infection and forms immune complexes, which enable the efficient infection of Fcγ receptor-bearing cells. However, the exact role played by Abs during a secondary infection of patients remains unknown. We previously obtained a broadly cross-reactive neutralizing IgG1 human monoclonal anti-DENV envelope (E) Ab (HuMAb) D23-1G7C2-IgG1 from a DENV-infected patient; however, D23-1G7C2-IgG1 had ADE activity. With the aim of being able to reduce the ADE activity, we exchanged the Fc region of D23-1G7C2 to generate Abs bearing each of the three other IgG subclasses (IgG2-4). In addition, N297A, a mutation known to reduce the affinity of the IgG1 Fc region for Fcγ receptors, was introduced into D23-1G7C2-IgG1. Swapping D23-1G7C2-IgG1 to IgG2 or IgG4 subclasses reduced ADE activity in FcγRI and FcγRII-bearing THP-1 cells. By contrast, in FcγRII-bearing K562 cells, the change to IgG2 increased ADE activity. Introducing the N297A mutation into D23-1G7C2-IgG1 resulted in a marked reduction in ADE activity in both cell types. Compared to D23-1G7C2-IgG1, D23-1G7C2-IgG1-N297A was less protective in IFN-α/β/γ receptor knockout mice infected with a lethal dose of recombinant chimeric DENV, carrying prME of DENV-2 in Japanese encephalitis virus (80% vs. 40% survival, respectively). These observations provide valuable information regarding the use of recombinant Abs as therapeutics.

  12. Lung in Dengue: Computed Tomography Findings

    OpenAIRE

    Rosana Souza Rodrigues; Ana Livia Garcia Brum; Marciano Viana Paes; Tiago Fajardo Póvoa; Carlos Alberto Basilio-de-Oliveira; Edson Marchiori; Danielle Provençano Borghi; Grazielle Viana Ramos; Fernando Augusto Bozza

    2014-01-01

    BACKGROUND: Dengue is the most important mosquito-borne viral disease in the world. Dengue virus infection may be asymptomatic or lead to undifferentiated fever, dengue fever with or without warning signs, or severe dengue. Lower respiratory symptoms are unusual and lung-imaging data in patients with dengue are scarce. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate lung changes associated with dengue infection, we retrospectively analyzed 2,020 confirmed cases of dengue. Twenty-nine of these pat...

  13. Associations between Dengue Hospitalizations and Climate in Can Tho, Vietnam, 2001-2011

    Directory of Open Access Journals (Sweden)

    Nguyen P. Toai

    2016-07-01

    Full Text Available In Vietnam, dengue fever is a major cause of hospitalization with over one million cases reported between 1991 and 2004. Changes in the incidence of dengue in Can Tho city due to increased temperature and changes in precipitation, are anticipated. In an effort to better characterize the relationship between climate and dengue, we examine the associations between weather variables and dengue hospitalizations in Can Tho between 2001 and 2011. Monthly data on hospitalized dengue cases and means of temperature, rainfall and humidity were recorded from 2001 to 2011. We used the Box-Jenkins approach to modelling of time series to assess the association between these factors. This model was validated by the Portmanteau test. Our results revealed that the highest dengue incidences in Can Tho occur between July and December. After adjusting for seasonality, the rate of dengue hospitalizations was significantly associated with relative humidity with a lag of one month. Rainfall and temperature were not predictors of dengue hospitalization rate. In conclusion, these data suggest that maximum relative humidity (with a one month lag is an important determinant of dengue hospitalizations. Enhanced vector control during months with high humidity may be an important approach to prevent dengue transmission.

  14. Age and Clinical Dengue Illness

    OpenAIRE

    Egger, Joseph R.; Paul G Coleman

    2007-01-01

    The relationship between age and risk for classic dengue fever has never been quantified. We use data from clinical patients to show that the relative risk of having classical disease after primary dengue virus infection increases with age. This relationship has implications for strategies aimed at controlling dengue fever.

  15. Acute brain hemorrhage in dengue

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2014-01-01

    Dengue is a tropical arboviral infection that can have severe hemorrhagic complication.Acute brain hemorrhage in dengue is rare and is a big challenge in neurosurgery.To perform surgery for management of acute brain hemorrhage in dengue is a controversial issue.Here, the authors try to summarize the previous reports on this topic and compare neurosurgery versus conservative management.

  16. Dengue encephalitis -a case report

    Institute of Scientific and Technical Information of China (English)

    P.C.Bhattacharyya; Jagdish Prasad Agarwal

    2009-01-01

    Encephalitis is an uncommon manifestation of dengue fever.Here we present a 4 years old female child from Northeast Region of India who suffered from dengue encephalitis.To our knowledge,this is probably the first diagnosed case of dengue fever from this region.

  17. MRI Findings In Dengue Encephalitis

    Directory of Open Access Journals (Sweden)

    Ashraf V.V

    2004-01-01

    Full Text Available Neurological manifestations are rare in dengue fever. Two cases with encephalopathy and systemic features of dengue fever with abnormal CSF and MR imaging are reported. Striking MRI finding was bilateral symmetrical thalamic lesions similar to those reported in Japanese encephalitis. This report highlights that MRI findings can be similar in dengue and Japanese encephalitis.

  18. The cancer process as a type of immunocomplex hypersensibility involving C3b, natural killer cytotoxicity and antibody-dependent cell cytotoxicity: proposals for tumour immunotherapy and vaccine.

    Science.gov (United States)

    Manzo, G

    1998-05-01

    I have previously assumed that stem tumour cells are 'para-embryonal cells' (PECs) poor or missing in major histocompatibility complex (MHC) antigens. PECs might induce adjoining differentiated hyperplastic cells to also express tumoral phenotype and properties, thus transforming them into 'differentiated para-embryonal cells' (DPECs), MHC-endowed. In such a way, PECs, MHC-lacking, would be automatically surrounded by DPECs, MHC-endowed: this tumour organization was experimentally found by Cordon-Cardo et al in a variety of cancers. Now, I suggest that such a tumour histology might preferentially induce an anti-DPEC T cell immune response which, sparing PECs, might release increasing amounts of DPEC antigens in the peritumour site. DPEC antigens might increase synthesis of specific antibodies and subsequent immunocomplex formation at the peritumour site. Here, abundant immunocomplexes might react through their Fc pieces with CD16 receptors of antibody-dependent cell cytotoxicity (ADCC)-endowed immune cells (natural killer (NK) cells, macrophages, polymorphonuclear cells). These cells would thus be stimulated to secrete their lytic factors before and without their coming into contact with target tumour cells. On the other hand, abundant immunocomplexes at the peritumour site might massively activate the complement system, thus generating large amounts of C3b. C3b might react with CD11b receptors of NK cells, stimulating them to also secrete their lytic factors in an ectopic way at the peritumour site, thus impairing NK cytotoxicity. In such a way, in the absence of ADCC and NK cytotoxicity, a tumour cell enhancement might easily occur. In the light of these ideas, a strategy for antitumour immunotherapy and vaccine is then proposed. PMID:9681920

  19. Dengue vaccine: an update on recombinant subunit strategies.

    Science.gov (United States)

    Martin, J; Hermida, L

    2016-03-01

    Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. There is no specific treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in recent years, an effective vaccine against the virus is not yet available. The development of a dengue vaccine has been hampered by many unique challenges, including the need to ensure the absence of vaccine-induced enhanced severity of disease. Recombinant protein subunit vaccines offer a safer alternative to other vaccine approaches. Several subunit vaccine candidates are presently under development, based on different structural and non-structural proteins of the virus. Novel adjuvants or immunopotentiating strategies are also being tested to improve their immunogenicity. This review summarizes the current status and development trends of subunit dengue vaccines. PMID:26982462

  20. Dengue vaccine: an update on recombinant subunit strategies.

    Science.gov (United States)

    Martin, J; Hermida, L

    2016-03-01

    Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. There is no specific treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in recent years, an effective vaccine against the virus is not yet available. The development of a dengue vaccine has been hampered by many unique challenges, including the need to ensure the absence of vaccine-induced enhanced severity of disease. Recombinant protein subunit vaccines offer a safer alternative to other vaccine approaches. Several subunit vaccine candidates are presently under development, based on different structural and non-structural proteins of the virus. Novel adjuvants or immunopotentiating strategies are also being tested to improve their immunogenicity. This review summarizes the current status and development trends of subunit dengue vaccines.

  1. Health beliefs and practices related to dengue fever: a focus group study.

    Directory of Open Access Journals (Sweden)

    Li Ping Wong

    Full Text Available BACKGROUND: This qualitative study aimed to provide an in-depth understanding of the meaning of dengue fever (DF amongst people living in a dengue endemic region, dengue prevention and treatment-seeking behaviours. The Health Belief Model was used as a framework to explore and understand dengue prevention behaviours. METHODS: A total of 14 focus group discussions were conducted with 84 Malaysian citizens of different socio-demographic backgrounds between 16(th December, 2011 and 12(th May, 2012. RESULTS: The study revealed that awareness about DF and prevention measures were high. The pathophysiology of dengue especially dengue haemorrhagic fever (DHF and dengue shock syndrome (DSS were rarely known; as a result, it was seen as deadly by some but was also perceived as easily curable by others without a basis of understanding. Young adults and elderly participants had a low perception of susceptibility to DF. In general, the low perceived susceptibility emerged as two themes, namely a perceived natural ability to withstand infection and a low risk of being in contact with the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self-prevention against dengue prevention that emerged in focus groups were: i lack of self-efficacy, ii lack of perceived benefit, iii low perceived susceptibility, and iv unsure perceived susceptibility. Low perceived benefit of continued dengue prevention practices was a result of lack of concerted action against dengue in their neighborhood. Traditional medical practices and home remedies were widely perceived and experienced as efficacious in treating DF. CONCLUSION: Behavioural change towards attaining sustainability in dengue preventive practices may be enhanced by fostering comprehensive knowledge of dengue and a change in health beliefs. Wide use of unconventional therapy for DF warrants the need to enlighten the public to limit their reliance on unproven alternative treatments.

  2. Practices of Dengue Fever Prevention and the Associated Factors among the Orang Asli in Peninsular Malaysia.

    Directory of Open Access Journals (Sweden)

    Josephine Rebecca Chandren

    Full Text Available Dengue is prevalent among Malaysia's indigenous peoples, known as the Orang Asli, and it poses a serious health threat to them. The study aims to look at the socio-demographic factors, health beliefs, and knowledge about dengue and its association to dengue prevention practices among Orang Asli communities in Peninsular Malaysia.A cross-sectional survey was conducted in 16 randomly selected Orang Asli villages from eight states in Peninsular Malaysia from April 2012 until February 2013.A total of 560 Orang Asli were interviewed and 505 completed the survey. Slightly above half of the participants (n = 280, 55.4% had a total dengue prevention score of 51-100 (of a possible score of 0-100. Multivariate analysis findings showed dengue knowledge, perceived barriers to perform dengue prevention, fogging frequency, and perceived susceptibility to dengue fever as significant factors associated to dengue prevention practices. Participants with a lower dengue knowledge score (score 0-18 were less likely (OR = 0.63, 95%CI = 0.44-0.92 vs. score 19-36, P = 0.015 to practice dengue prevention. Participants with low perceived barriers to prevent dengue (score of 1-5 were more likely (OR = 2.06, 95%CI = 1.21-3.53, vs. score of 6-10, P = 0.008 to practice dengue prevention. Villages that were not fogged (OR = 0.49, 95%CI = 0.24-0.99, P = 0.045 or rarely fogged (OR = 0.40, 95%CI = 0.22-0.75, P = 0.004 had lower dengue prevention practices than villages that were fogged often. Participants with low perceived susceptibility of acquiring dengue (score of 1-5 were less likely (OR = 0.54, 95%CI = 0.33-0.89 vs. score of 6-10, P = 0.018 to practice dengue prevention measures.Findings imply that educational and health programmes should focus on enhancing dengue knowledge and perceived susceptibility of acquiring dengue and reducing perceived barriers to performing dengue prevention practices among the Orang Asli. More outreach on mosquito control campaigns should be

  3. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G;

    2013-01-01

    not covered by immunological tolerance in MUC1 humanized mice and man. The objective of this study was to determine if mouse antibodies to this Tn-MUC1 epitope induce antibody-dependent cellular cytotoxicity (ADCC) pivotal for their potential use in cancer immunotherapy. Binding affinity of mAb 5E5 directed...

  4. Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark.

    Science.gov (United States)

    Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Palm, Angelica A; Gerstoft, Jan; Kronborg, Gitte; Hønge, Bo Langhoff; Jespersen, Sanne; da Silva, Zacarias José; Karlsson, Ingrid; Fomsgaard, Anders

    2016-05-01

    The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine. PMID:26621287

  5. Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.

    Science.gov (United States)

    Silveira, G F; Strottmann, D M; de Borba, L; Mansur, D S; Zanchin, N I T; Bordignon, J; dos Santos, C N Duarte

    2016-01-01

    Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV.

  6. Micronutrients and dengue.

    Science.gov (United States)

    Ahmed, Sundus; Finkelstein, Julia L; Stewart, Anna M; Kenneth, John; Polhemus, Mark E; Endy, Timothy P; Cardenas, Washington; Mehta, Saurabh

    2014-11-01

    Dengue virus infection is the most widespread mosquito-borne viral infection in humans and has emerged as a serious global health challenge. In the absence of effective treatment and vaccine, host factors including nutritional status, which may alter disease progression, need investigation. The interplay between nutrition and other infections is well-established, and modulation of nutritional status often presents a simple low-cost method of interrupting transmission, reducing susceptibility, and/or ameliorating disease severity. This review examines the evidence on the role of micronutrients in dengue virus infection. We found critical issues and often inconsistent results across studies; this finding along with the lack of sufficient literature in this field have limited our ability to make any recommendations. However, vitamins D and E have shown promise in small supplementation trials. In summary, the role of micronutrients in dengue virus infection is an exciting research area and needs to be examined in well-designed studies with larger samples.

  7. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G;

    2012-01-01

    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage....... As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use...... of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...

  8. [Maculopathy and dengue fever].

    Science.gov (United States)

    Jellab, B; Fardeau, C; Lehoang, P

    2013-01-01

    The authors report a case of a 20 year old female who presented a bilateral decrease in vision. Detailed history revealed that 15 days before the onset of symptoms, the patient presented a dengue fever during her stay in Martinique. On initial examination, the fundus exam revealed a bilateral loss of foveal reflection. The optical coherence tomography demonstrated the macular edema and the dengue serology was postive. The patient received an interferon2a-based therapy. The macular edema disappeared and we noticed a partial but fast improvement of visual acuity 12 days after the treatment initiation. PMID:24923080

  9. DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER IN ADULTS.

    Science.gov (United States)

    Tantawichien, Terapong

    2015-01-01

    Dengue fever and dengue hemorrhagic fever are re-emerging diseases that are endemic in the Tropics. The global prevalence of dengue cases has increased in South-East Asia, Africa, the Western Pacific, and the Americas. The increasingly widespread distribution and the rising incidence of dengue virus infections are related to increased distribution of Aedes aegypti, an increasingly urban population, and increasing air travel. Several Southeast Asian countries show that the age of the reported dengue cases has increased from 5-9 years, to older children and young adults. Dengue infection in adolescents and adults has also been recognized as a potential hazard to international travelers returning from endemic areas, especially SoutheastAsia. Dengue is one disease entity with different clinical presentations; often with unpredictable clinical evolutions and outcomes. Bleeding manifestations in adult patients, including petechiae and menorrhagia were also frequently found; however, massive hematemesis may occur in adult patients because of peptic ulcer disease and may not be associated with profound shock as previously reported in children. Although shock and plasma leakage seem to be more prevalent as age decreases, the frequency of internal hemorrhage rises as age increases. Increase in liver enzymes found in both children and adults indicated liver involvement during dengue infections. Pre-existing liver diseases in adults such as chronic hepatitis, alcoholic cirrhosis, and hemoglobinopathies may aggravate the liver impairment in dengue infection. Fulminant hepatitis is a rare but well described problem in adult patients with dengue infection. Currently, no specific therapeutic agent exists for dengue. The early recognition of dengue infection, bleeding tendency, and signs of circulatory collapse would reduce mortality rates in adult patients with dengue infection. PMID:26506734

  10. The Hidden Burden of Dengue and Chikungunya in Chennai, India.

    Directory of Open Access Journals (Sweden)

    Isabel Rodríguez-Barraquer

    Full Text Available Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission.We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio and IgG ELISA (Novatec, respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95% of participants were seropositive to dengue virus, and 44% (95%CI 37-50% to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas.These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods.

  11. Dengue serosurvey in Sint Eustatius.

    Directory of Open Access Journals (Sweden)

    Teresa Leslie

    Full Text Available Four distinct serotypes of dengue viruses (DENV are the cause of re-emerging dengue fever (DF and dengue hemorrhagic fever (DHF. Dengue circulation in the Caribbean has gone from none or single serotype to multiple serotypes co-circulating with reports of continuing cycles of progressively more severe disease in the region. Few studies have investigated dengue on Sint Eustatius. Blood samples were collected to determine the prevalence of antibodies against dengue in the Sint Eustatius population. Greater than 90% of the serum samples (184 of 204 were positive for anti-flavivirus antibodies by enzyme linked immunosorbance assay (ELISA. Plaque reduction neutralization test (PRNT, specific for dengue viruses, showed that 171 of these 184 flavivirus antibody positive sera had a neutralization titer against one or more DENV serotypes. A majority of the sera (62% had neutralizing antibody to all four dengue serotypes. Only 26 PRNT positive sera (15% had monotypic dengue virus neutralizing antibody, most of which (20 of 26 were against DENV2. Evidence of infection with all four serotypes was observed across all age groups except in the youngest age group (10-19 years which contained only DENV2 positive individuals. In a multiple logistic regression model, only the length of residence on the island was a predictor of a positive dengue PRNT50 result. To our knowledge this is the first dengue serosurveillance study conducted on Sint Eustatius since the 1970s. The lack of antibodies to the DEN1, 3, and 4 in the samples collected from participants under 20 years of age suggests that only DEN2 has circulated on island since the early 1990s. The high prevalence of antibodies against dengue (83.8% and the observation that the length of time on the island was the strongest predictor of infection suggests dengue is endemic on Sint Eustatius and a public health concern that warrants further investigation.

  12. Introducing dengue vaccine: Implications for diagnosis in dengue vaccinated subjects.

    Science.gov (United States)

    Alagarasu, Kalichamy

    2016-05-27

    Diagnosis of dengue virus infections is complicated by preference for different diagnostic tests in different post onset days of illness and the presence of multiple serotypes leading to secondary and tertiary infections. The sensitivity of the most commonly employed diagnostic assays such as anti dengue IgM capture (MAC) ELISA and non structural protein (NS) 1 capture ELISA are lower in secondary and subsequent infections. Introduction of dengue vaccine in endemic regions will affect the way how dengue is diagnosed in vaccinated subjects. This viewpoint article discusses implications of introduction of dengue vaccine on the diagnosis of dengue infections in vaccinated subjects and the strategies that are needed to tackle the issue. PMID:27142330

  13. Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy.

    Science.gov (United States)

    Trotta, Anna Maria; Ottaiano, Alessandro; Romano, Carmela; Nasti, Guglielmo; Nappi, Anna; De Divitiis, Chiara; Napolitano, Maria; Zanotta, Serena; Casaretti, Rossana; D'Alterio, Crescenzo; Avallone, Antonio; Califano, Daniela; Iaffaioli, Rosario Vincenzo; Scala, Stefania

    2016-04-01

    Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcγ receptors on immune cells. Although SNPs in genes encoding Fcγ receptors are functionally relevant to cetuximab-mediated ADCC in colorectal cancer, a direct correlation betweenin vitroADCC and clinical response to cetuximab is not defined. We therefore enrolled 96 consecutive metastatic colorectal cancer (mCRC) patients at diagnosis in a study that assessed FcγR status and cetuximab-mediated ADCC. Patients carrying the FcγRIIaHalleles 131H/Hand 131H/Rhad significantly higher ADCC compared with patients with the 131R/Ralleles (P= 0.013). Patients carrying FcγRIIIa genotypes with theValleles 158V/Vand 158V/Fdisplayed higher ADCC compared with patients carrying the 158F/Fgenotype (P= 0.001). Progression-free survival of patients with an FcγRIIIa 158Vallele was significantly longer compared with patients carrying 158F/F(P= 0.05), whereas no significant difference was observed for overall survival. Twenty-eight of 50 mCRC patients with wild-type KRAS received cetuximab. The average ADCC-mediated killing was 30% of assay targets for patients who experienced cetuximab complete or partial response, 21% in patients with stable disease and 9% in patients with progressive disease. To characterize basal natural killer (NK) activity, cytotoxicity was evaluated in 39 of 96 mCRC patients. Patients who responded to first-line treatment had higher NK-cell cytotoxicity. Thus, although limited to this cohort of patients,in vitrocetuximab-mediated ADCC correlated with FcγR polymorphisms and predicted cetuximab responsiveness.Cancer Immunol Res; 4(4); 366-74. ©2016 AACR. PMID:26817995

  14. The Role of Serotype Interactions and Seasonality in Dengue Model Selection and Control: Insights from a Pattern Matching Approach.

    Science.gov (United States)

    Ten Bosch, Quirine A; Singh, Brajendra K; Hassan, Muhammad R A; Chadee, Dave D; Michael, Edwin

    2016-05-01

    The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control. PMID:27159023

  15. [Dengue, Zika and Chikungunya].

    Science.gov (United States)

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  16. [Dengue, Zika and Chikungunya].

    Science.gov (United States)

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation. PMID:26942903

  17. A Dengue Vaccine.

    Science.gov (United States)

    Durbin, Anna P

    2016-06-30

    Denvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year. PMID:27368091

  18. Dengue Fever Testing

    Science.gov (United States)

    ... the initial fever has passed. Antibody tests for dengue fever can be positive if a person is infected with another arbovirus such as West Nile virus . A health practitioner will consider a person's test results, medical history, and recent travel history in making a diagnosis. ...

  19. Dengue haemorrhagic fever or dengue shock syndrome in children

    OpenAIRE

    Alejandria, Marissa M

    2009-01-01

    Infection with the dengue virus, transmitted by mosquito, ranges from asymptomatic or undifferentiated febrile illness to fatal haemorrhagic fever, and affects up to 100 million people a year worldwide. Dengue haemorrhagic fever is characterised by: a sudden onset of high fever; haemorrhages in the skin, gastrointestinal tract, and mucosa; and low platelet counts. Plasma leakage results in fluid in the abdomen and lungs. It typically occurs in children under 15 years.Severe dengue haemorrh...

  20. Dengue fever and dengue haemorrhagic fever in adolescents and adults

    OpenAIRE

    Tantawichien, Terapong

    2012-01-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a...

  1. A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion.

    Science.gov (United States)

    Shi, Xin; Deng, Yongqiang; Wang, Huajing; Ji, Guanghui; Tan, Wenlong; Jiang, Tao; Li, Xiaofeng; Zhao, Hui; Xia, Tian; Meng, Yanchun; Wang, Chao; Yu, Xiaojie; Yang, Yang; Li, Bohua; Qin, E-De; Dai, Jianxin; Qin, Cheng-Feng; Guo, Yajun

    2016-01-01

    Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV. PMID:26905804

  2. Dengue: where are we today?

    OpenAIRE

    Guzman, Maria Guadalupe; Vázquez, Susana; Kouri, Gustavo

    2009-01-01

    Dengue is considered the main arthropod-borne viral disease of humans. In the last few years, an increasing number of reports of mild and severe cases have been reported. The growing dengue incidence observed in recent years has been accompanied by reports of new observations, findings and global initiatives with an improvement in our understanding of this phenomenon. The epidemiology and new clinical classification of dengue, advances in the diagnostic and pathogenesis knowledge, and vaccine...

  3. Dengue research opportunities in the Americas.

    Science.gov (United States)

    Laughlin, Catherine A; Morens, David M; Cassetti, M Cristina; Costero-Saint Denis, Adriana; San Martin, Jose-Luis; Whitehead, Stephen S; Fauci, Anthony S

    2012-10-01

    Dengue is a systemic arthropod-borne viral disease of major global public health importance. At least 2.5 billion people who live in areas of the world where dengue occurs are at risk of developing dengue fever (DF) and its severe complications, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Repeated reemergences of dengue in sudden explosive epidemics often cause public alarm and seriously stress healthcare systems. The control of dengue is further challenged by the lack of effective therapies, vaccines, and point-of-care diagnostics. Despite years of study, even its pathogenic mechanisms are poorly understood. This article discusses recent advances in dengue research and identifies challenging gaps in research on dengue clinical evaluation, diagnostics, epidemiology, immunology, therapeutics, vaccinology/clinical trials research, vector biology, and vector ecology. Although dengue is a major global tropical pathogen, epidemiologic and disease control considerations in this article emphasize dengue in the Americas. PMID:22782946

  4. Ongoing outbreak of dengue serotype-3 in Solomon Islands, January to May 2013

    Directory of Open Access Journals (Sweden)

    Francisco Nogareda

    2013-07-01

    Full Text Available Introduction: In January 2013, clinicians in Honiara, Solomon Islands noted several patients presenting with dengue-like illness. Serum from three cases tested positive for dengue by rapid diagnostic test. Subsequent increases in cases were reported, and the outbreak was confirmed as being dengue serotype-3 by further laboratory tests. This report describes the ongoing outbreak investigation, findings and response. Methods: Enhanced dengue surveillance was implemented in the capital, Honiara, and in the provinces. This included training health staff on dengue case definitions, data collection and reporting. Vector surveillance was also conducted. Results: From 3 January to 15 May 2013, 5254 cases of suspected dengue were reported (101.8 per 10 000 population, including 401 hospitalizations and six deaths. The median age of cases was 20 years (range zero to 90, and 86% were reported from Honiara. Both Aedes aegyti and Aedes albopictus were identified in Honiara. Outbreak response measures included clinical training seminars, vector control activities, implementation of diagnostic and case management protocols and a public communication campaign. Discussion: This was the first large dengue outbreak documented in Solomon Islands. Factors that may have contributed to this outbreak include a largely susceptible population, the presence of a highly efficient dengue vector in Honiara, a high-density human population with numerous breeding sites and favourable weather conditions for mosquito proliferation. Although the number of cases has plateaued since 1 April, continued enhanced nationwide surveillance and response activities are necessary.

  5. Dengue Disease Spectrum among Infants in the 2001 Dengue Epidemic in Chennai, Tamil Nadu, India

    OpenAIRE

    Kabilan, L; Balasubramanian, S.; Keshava, S. M.; Thenmozhi, V.; Mr G.Sekar; S. C. Tewari; N. Arunachalam; Rajendran, R.; Satyanarayana, K.

    2003-01-01

    An investigation in a referral pediatric hospital has indicated that during a recent dengue outbreak in Chennai, Tamil Nadu, India, dengue in infancy constituted 20% of total dengue virus infections with low mortality rates in this hospital. In developing countries, strengthening of dengue management capabilities at hospitals can prevent dengue-related deaths in infants.

  6. Antibody-dependent cell-mediated cytotoxicity (ADCC) toward human O+ red cells coated with anti-D antibody: comparison between lymphocyte and monocyte ADCC activity.

    OpenAIRE

    Sunada,Mitsutoshi; Suzuki, Shinya; Ota, Zensuke

    1985-01-01

    We investigated the antibody dependent cell-mediated cytotoxicity (ADCC) of lymphocytes and monocytes toward human O+ red cells coated with anti-D antibody using a 51Cr release assay. Lysis of sensitized red cells by lymphocytes occurred rapidly, but monocyte-mediated lysis occurred slowly. This difference might be due to postphagocytic 51Cr release by monocytes. ADCC of lymphocytes increased in proportion to the effector cell number, but large amounts of antibodies were required. In contrast...

  7. Development of IgG Mediated Antibody Dependent Cell-mediated Cytotoxicity (ADCC) in the Serum and Genital Mucosa of HIV Seroconverters

    OpenAIRE

    Aziz, Mariam; Mahmood, Fareeha; Mata, Mariana; Durkin, Helen G.; Liu, Chenglong; Greenblatt, Ruth M.; Nowicki, Marek; Elizabeth T Golub; Anastos, Kathryn; French, Audrey L.; Baum, Linda L.

    2015-01-01

    Background We measured antibody-dependent cell mediated cytotoxicity (ADCC) activity in serum and genital fluids of heterosexually exposed women during HIV seroconversion. Methods Plasma and cervico-vaginal lavage (CVL) fluid from 11 seroconverters (SC) were analyzed biannually from one year pre- to 6 year post-seroconversion using a 51Cr-release assay to measure HIV-1 gp120 specific ADCC. Results No SC had significant HIV specific CVL ADCC activity before seroconversion or until 1.5 yr after...

  8. On the risk of severe dengue during secondary infection: A systematic review coupled with mathematical modeling

    Directory of Open Access Journals (Sweden)

    Kenji Mizumoto

    2014-08-01

    Full Text Available Background & objectives: The present study aimed to systematically quantify the well known risk of severe dengue during secondary infection in literature and to understand how epidemiological mechanisms of enhancement during the secondary infection influence the empirically estimated risk of severe dengue by means of mathematical modeling. Methods: Two conditional risks of severe dengue, i.e. symptomatic illness and dengue hemorrhagic fever (DHF or dengue shock syndrome (DSS, given secondary infection were explored based on systematically searched prospective studies. A two-strain epidemiological model was employed to simulate the transmission dynamics of dengue and to identify the relevant data gaps in empirical observations. Results: Using the variance-based weighting, the pooled relative risk (RR of symptomatic illness during secondary infection was estimated at 9.4 [95% confidence interval (CI: 6.1-14.4], and similarly, RR of DHF/DSS was estimated to be 23.7 (95% CI: 15.3-36.9. A variation in the RR of DHF/DSS was observed among prospective studies. Using the mathematical modeling technique, we identified the duration of cross-protective immunity as an important modulator of the time-dependent behaviour of the RR of severe dengue. Different epidemiological mechanisms of enhancement during secondary infection yielded different RR of severe dengue. Interpretation & conclusion: Optimal design of prospective cohort study for dengue should be considered, accounting for the time-dependence in the RR during the course of dengue epidemic. It is critical to statistically infer the duration of cross-protective immunity and clarify how the enhancement influences the epidemiological dynamics during secondary infection.

  9. Overview of current situation of dengue and dengue vector control

    Science.gov (United States)

    Dengue is the most important arbovirus of humans in the world. It is caused by one of four closely related virus serotypes whose primary vector is Aedes aegypti and secondarily by Ae. albopictus. A global dengue pandemic began in Southeast Asia after World War II and has intensified during the las...

  10. Dengue fever with acute liver failure

    OpenAIRE

    Vinodh B; Bammigatti C; Kumar Ashok; Mittal V

    2005-01-01

    A virus belonging to the Flaviviridae group causes dengue haemorrhagic fever. Dengue presenting as acute liver failure is rare. Dengue is endemic in India. The last epidemic of dengue occurred in Delhi in 2003. During this epidemic, 2185 confirmed cases of dengue were reported. Dengue virus serotypes 2 and 3 were responsible for this epidemic. A 19-yr-old male presented to our hospital with the complaints of fever for 12 days, during this epidemic. He was diagnosed as having dengue shock synd...

  11. Prospects for dengue vaccines for travelers

    Science.gov (United States)

    2016-01-01

    Travel-acquired dengue cases have been increasing as the overall global dengue burden has expanded. In Korea, imported dengue cases have been reported since 2000 when it first became a notifiable disease. During the first four months of 2016, three times more dengue cases were reported in Korea than during the same period the previous year. A safe and efficacious vaccine for travelers would be beneficial to prevent dengue disease in individual travelers and potentially decrease the risk of virus spread to non-endemic areas. Here, we summarize the characteristics of dengue vaccines for travelers and review dengue vaccines currently licensed or in clinical development. PMID:27489798

  12. Prospects for dengue vaccines for travelers.

    Science.gov (United States)

    Lim, Sl-Ki; Lee, Yong Seok; Namkung, Suk; Lim, Jacqueline K; Yoon, In-Kyu

    2016-07-01

    Travel-acquired dengue cases have been increasing as the overall global dengue burden has expanded. In Korea, imported dengue cases have been reported since 2000 when it first became a notifiable disease. During the first four months of 2016, three times more dengue cases were reported in Korea than during the same period the previous year. A safe and efficacious vaccine for travelers would be beneficial to prevent dengue disease in individual travelers and potentially decrease the risk of virus spread to non-endemic areas. Here, we summarize the characteristics of dengue vaccines for travelers and review dengue vaccines currently licensed or in clinical development. PMID:27489798

  13. Dengue-1 Virus Isolation during First Dengue Fever Outbreak on Easter Island, Chile

    OpenAIRE

    Perret, Cecilia; Abarca, Katia; Ovalle, Jimena; Ferrer, Pablo; Godoy, Paula; Olea, Andrea; Aguilera, Ximena; Ferrés, Marcela

    2003-01-01

    Dengue virus was detected for the first time in Chile, in an outbreak of dengue fever on Easter Island. The virus was isolated in tissue culture and characterized by reverse transcription–polymerase chain reaction as being dengue type 1.

  14. Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions.

    Directory of Open Access Journals (Sweden)

    James Whitehorn

    2014-08-01

    Full Text Available Dengue is the most common arboviral disease of humans. There is an unmet need for a therapeutic intervention that reduces the duration and severity of dengue symptoms and diminishes the likelihood of severe complications. To this end, there are active discovery efforts in industry and academia to develop interventions, with a focus on small molecule inhibitors of dengue virus replication that are suitable for therapy or chemoprophylaxis. Advancements in animal models of dengue virus infection together with the possibility of a dengue human infection model have further enhanced the platform for dengue drug discovery. Whilst drug discovery efforts gestate, there are ongoing clinical research designed to benefit today's patients, including trials of supportive care interventions, and descriptive studies that should improve the ability of clinicians to make an accurate diagnosis early in the illness course and to identify patients most at risk of progression to severe disease. This review provides a state of the art summary of dengue drug discovery, clinical trials, and supportive allied research and reflects discussions at the 2nd International Dengue Therapeutics Workshop held in Ho Chi Minh City, Vietnam, in December 2013.

  15. Transfusion support in patients with dengue fever

    OpenAIRE

    Kaur, Paramjit; Kaur, Gagandeep

    2014-01-01

    Dengue fever has emerged as a global public health problem in the recent decades. The clinical spectrum of the disease ranges from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. The disease is characterized by increased capillary permeability, thrombocytopenia and coagulopathy. Thrombocytopenia with hemorrhagic manifestations warrants platelet transfusions. There is lack of evidence-based guidelines for transfusion support in patients with dengue fever. This contributes t...

  16. Lessons learned from previous dengue outbreaks

    OpenAIRE

    Wiwanitkit, Viroj

    2014-01-01

    Dengue is an important tropical infection caused by an arbovirus dengue. As a mosquito borne infection, this disease is widely spread in several tropical endemic countries. Millions of world populations are at risk for this arboviral infection. Each year, thousands of dengue infections are reported and there are several death cases. Each year, the outbreaks of dengue emerge in several countries and this implies the global importance of this infection. Fighting with dengue outbreak is importan...

  17. Dengue Fever, Hawaii, 2001–2002

    OpenAIRE

    Effler, Paul V.; Pang, Lorrin; Kitsutani, Paul; Vorndam, Vance; Nakata, Michele; Ayers, Tracy; Elm, Joe; Tom, Tammy; Reiter, Paul; Rigau-Perez, José G.; Hayes, John M; Mills, Kristin; Napier, Mike; Clark, Gary G.; Gubler, Duane J.

    2005-01-01

    Autochthonous dengue infections were last reported in Hawaii in 1944. In September 2001, the Hawaii Department of Health was notified of an unusual febrile illness in a resident with no travel history; dengue fever was confirmed. During the investigation, 1,644 persons with locally acquired denguelike illness were evaluated, and 122 (7%) laboratory-positive dengue infections were identified; dengue virus serotype 1 was isolated from 15 patients. No cases of dengue hemorrhagic fever or shock s...

  18. Seropositivity of Dengue Antibodies during Pregnancy

    OpenAIRE

    Nor Azlin Mohamed Ismail; Wan Elly Rushima Wan Abd Rahim; Sharifah Azura Salleh; Hui-Min Neoh; Rahman Jamal; Muhammad Abdul Jamil

    2014-01-01

    Purpose. Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM) during pregnancy and its neonatal transmission in dengue seropositive women. Methods. Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM) using an enzyme-linked immunosorbent assay (ELISA). Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal A...

  19. Dot enzyme immunoassay: an alternative diagnostic aid for dengue fever and dengue haemorrhagic fever.

    OpenAIRE

    Cardosa, M. J.; Tio, P. H.

    1991-01-01

    A dot enzyme immunoassay (DEIA) for the detection of antibodies to dengue virus was tested for use as a tool in the presumptive diagnosis of dengue fever and dengue haemorrhagic fever. Paired sera from the following groups of patients were tested using the DEIA and the haemagglutination inhibition (HI) test: those with primary dengue fever; those experiencing a second dengue infection; and febrile patients who did not have dengue. The data obtained show that the DEIA can be effectively used a...

  20. Monoclonal antibody to dengue capsid protein: Its application in dengue studies

    OpenAIRE

    Vazquez, Y; Pupo-Antúnez, Maritza; Vazquez, S V; Capó,; Torres, G.; Caballero, Y.; A Sánchez; Limonta, D; Alvarez, M.; Guzmán, MG

    2009-01-01

    Dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are considered the most important arthropod-borne viral diseases in terms of morbidity and mortality. The emergency and severity of dengue (Den) infections increase the necessity of an early, quick and effective dengue laboratory diagnostic. Viral isolation is considered a gold standard for diagnosis of dengue infection using monoclonal antibodies (mAbs) as a tool for determining serotype specificity. Alternatives ...

  1. Perbedaan Kadar Platelet Activating Factor Plasma antara Penderita Demam Berdarah Dengue dan Demam Dengue

    OpenAIRE

    Djatnika Setiabudi; Budi Setiabudiawan; Ida Parwati; Herry Garna

    2013-01-01

    Dengue virus infection can manifest as dengue fever and, more severely, as dengue hemorrhagic fever. Their pathogenesis until now is not fully understood. One of the most favorable theories stated the presence of increasing titer of pro-inflammatory mediator in severe dengue. The aim of this study was to determine the difference of plasma platelet activating factor titer between dengue hemorrhagic fever and dengue fever patients. This observational study with cross sectional design was conduc...

  2. Dynamic spatiotemporal trends of imported dengue fever in Australia

    Science.gov (United States)

    Huang, Xiaodong; Yakob, Laith; Devine, Gregor; Frentiu, Francesca D.; Fu, Shiu-Yun; Hu, Wenbiao

    2016-01-01

    Dengue fever (DF) epidemics in Australia are caused by infected international travellers and confined to Northern Queensland where competent vectors exist. Recent analyses suggest that global trade and climate change could lead to the re-establishment of Ae. aegypti across the country and promote the spread of dengue nationally. This study aimed to describe the dynamic spatiotemporal trends of imported DF cases and their origins, identify the current and potential future high-risk regions and locate areas that might be at particular risk of dengue transmission should competent mosquito vectors expand their range. Our results showed that the geographical distribution of imported DF cases has significantly expanded in mainland Australia over the past decade. In recent years, the geographical distribution of source countries of DF has expanded from the Pacific region and Asia to include Africa and the Americas. Australia is now exposed to dengue importations from all of the regions involved in the current global pandemic. The public health implications of a range expansion of dengue mosquito vectors are severe. Enhanced mosquito surveillance in those areas that have high imported cases is called for to reduce emerging threats from this globally expanding pathogen. PMID:27460696

  3. A critical assessment of vector control for dengue prevention.

    Directory of Open Access Journals (Sweden)

    Nicole L Achee

    2015-05-01

    Full Text Available Recently, the Vaccines to Vaccinate (v2V initiative was reconfigured into the Partnership for Dengue Control (PDC, a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1 a critical assessment of current vector control tools and those under development, (2 outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3 determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations.

  4. Dynamic spatiotemporal trends of imported dengue fever in Australia.

    Science.gov (United States)

    Huang, Xiaodong; Yakob, Laith; Devine, Gregor; Frentiu, Francesca D; Fu, Shiu-Yun; Hu, Wenbiao

    2016-01-01

    Dengue fever (DF) epidemics in Australia are caused by infected international travellers and confined to Northern Queensland where competent vectors exist. Recent analyses suggest that global trade and climate change could lead to the re-establishment of Ae. aegypti across the country and promote the spread of dengue nationally. This study aimed to describe the dynamic spatiotemporal trends of imported DF cases and their origins, identify the current and potential future high-risk regions and locate areas that might be at particular risk of dengue transmission should competent mosquito vectors expand their range. Our results showed that the geographical distribution of imported DF cases has significantly expanded in mainland Australia over the past decade. In recent years, the geographical distribution of source countries of DF has expanded from the Pacific region and Asia to include Africa and the Americas. Australia is now exposed to dengue importations from all of the regions involved in the current global pandemic. The public health implications of a range expansion of dengue mosquito vectors are severe. Enhanced mosquito surveillance in those areas that have high imported cases is called for to reduce emerging threats from this globally expanding pathogen. PMID:27460696

  5. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics.

  6. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. PMID:26424605

  7. DENGUE VACCINE, CHALLENGES, DEVELOPMENT AND STRATEGIES

    Directory of Open Access Journals (Sweden)

    Dewi Marbawati

    2014-08-01

    Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency

  8. Of cascades and perfect storms: the immunopathogenesis of dengue haemorrhagic fever-dengue shock syndrome (DHF/DSS).

    Science.gov (United States)

    Pang, Tikki; Cardosa, Mary Jane; Guzman, Maria G

    2007-01-01

    The past four decades has witnessed a consolidation of the original observations made in the 1970s that dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) have an immunological basis. Following reinfection with a dengue virus of different serotype, severe disease is linked to high levels of antibody-enhanced viral replication early in illness which is followed by a cascade of memory T-cell activation and a 'storm' of inflammatory cytokines and other chemical mediators. These compounds are released mainly from T cells, monocytes/macrophages and endothelial cells, and ultimately cause an increase in vascular permeability. The consolidation of the evidence has been largely due to several important prospective sero-epidemiological studies in areas endemic for DHF/DSS, which have shown that risk of severe disease is significantly higher in secondary dengue infections. These advances have underscored the fact that DHF/DSS pathogenesis is a complex, multifactorial process involving cocirculation of various dengue virus serotypes and the interplay of host and viral factors that influence disease severity. The continued search to define risk factors in susceptible populations must be combined with the new techniques of molecular virology and innovative approaches in vaccine design to achieve the ultimate objective of developing a safe and effective vaccine. PMID:17130899

  9. [Population genetics of dengue virus and transmission of dengue fever].

    Science.gov (United States)

    Falcón-Lezama, Jorge; Sánchez-Burgos, Gilma Guadalupe; Ramos-Castañeda, José

    2009-01-01

    The endemic behavior of dengue fever in Mexico during the past five years is of major concern to every sector related with public health and the effort to control the transmission has been focused on vector control. However, regardless of the effectiveness of the intervention measures it is important to know which elements determine dengue transmission. With regard to the molecular basis for dengue transmission, a great deal of progress has been made due to the introduction of genomic and bioinformatic approaches. The goal of this review is to describe the most recent developments in this area with emphasis on the Mexican situation.

  10. Ecg manifestations in dengue infection

    International Nuclear Information System (INIS)

    To determine the frequency of ECG changes in patients with dengue fever and dengue hemorrhagic fever. Place of study: Department of Medicine, Mayo Hospital Lahore Duration of study: September to November 201 Study design: Cross sectional analytical study Patient and methods: 116 patients with dengue infection were enrolled in the study. Their clinical presentation and examination was duly noted. Each patient had baseline and then regular monitoring of blood counts, metabolic profile and fluid status. Patients with Dengue Hemorrhagic fever underwent radiological examination in form of chest radiograph and ultrasound abdomen. ECG was carried out in all patients. Results: Out of 116 patients, 61(52.6%) suffered from Dengue Fever and 55(47.4%) had Dengue Hemorrhagic Fever. Overall 78 patients had normal ECG. Abnormal ECG findings like tachycardia, bradycardia, supraventricular tachycardia, left bundle branch block, ST depression, poor progression of R wave were noted. There was no significant relationship of ECG findings with the disease. Conclusion: ECG changes can occur in dengue infection with or without cardiac symptoms. Commonly noted findings were ST depression and bradycardia. (author)

  11. Dengue epidemiology in Thanjavur and Trichy district, Tamilnadu - Jan 2011-Dec 2011

    Directory of Open Access Journals (Sweden)

    Chinnathambi Kalidoss Bhuvaneswari

    2011-01-01

    Full Text Available Background: Dengue infection is emerging as a serious public health problem in Tamil Nadu. An enhanced surveillance system can generate information on the epidemiology of the disease, which is essential for planning and development of relevant control/preventive measures against Dengue. Materials and Methods: A prospective descriptive study was undertaken between January 2011 to December 2011, by testing suspected Dengue patients attending Thanjavur Medical College and Trichy Hospital (TMCH, a major Government referral hospital in Thanjavur District, Tamil Nadu, India to define the magnitude of Dengue burden, the natural history of this disease in terms of clinical presentation and outcome of the infections in hospitalized Dengue patients. The sera collected from suspected patients were analyzed for Dengue specific IgM and IgG antibodies by IgM antibody capture enzyme linked immunosorbent assay (ELISA using NIV kit and IgGPanBio Duo Rapid Immunochromatographic Card Test (Brisbane, Australia. The clinical case definition by World Health Organization was adopted to categorize the Dengue cases. Results: The total number of samples screened during the period was 200, out of which 79 (39.5% were positive for IgM and IgG antibodies and 65 (32% for IgM antibodies only. By clinical evaluation, Dengue fever was diagnosed in 43 patients, 18 had hemorrhagic manifestations and four patients had progressed to DSS. Though (DSS + DHF was present in 22 patients, all of them recovered well. Conclusion: In developing countries like India, building of laboratory with advanced capacity for diagnosis and combat-mode ready preparedness for the management of Dengue cases in emergency situation may reduce Dengue-related mortality.

  12. HIV-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) -Mediating Antibodies Decline while NK Cell Function Increases during Antiretroviral Therapy (ART)

    DEFF Research Database (Denmark)

    Skov Jensen, Sanne; Fomsgaard, Anders; Borggren, Marie;

    2015-01-01

    Understanding alterations in HIV-specific immune responses during antiretroviral therapy (ART), such as antibody-dependent cellular cytotoxicity (ADCC), is important in the development of novel strategies to control HIV-1 infection. This study included 53 HIV-1 positive individuals. We evaluated...... the ability of effector cells and antibodies to mediate ADCC separately and in combination using the ADCC-PanToxiLux assay. The ability of the peripheral blood mononuclear cells (PBMCs) to mediate ADCC was significantly higher in individuals who had been treated with ART before seroconversion, compared...... to the individuals initiating ART at a low CD4+ T cell count (antibodies mediating ADCC declined...

  13. Dengue virus. Fast Diagnosis of dengue virus by molecular analysis

    International Nuclear Information System (INIS)

    This article is about a regional project in the assurance and quality control of molecular diagnosis. It allows the identification of parasites genotypes that infect humans, particularly dengue that is a viral disease transmitted by mosquitoes

  14. Post-dengue encephalopathy and Parkinsonism.

    Science.gov (United States)

    Fong, Choong Yi; Hlaing, Chaw Su; Tay, Chee Geap; Ong, Lai Choo

    2014-10-01

    Parkinsonism as a neurologic manifestation of dengue infection is rare with only 1 reported case in an adult patient. We report a case of a 6-year-old child with self-limiting post-dengue encephalopathy and Parkinsonism. This is the first reported pediatric case of post-dengue Parkinsonism and expands the neurologic manifestations associated with dengue infection in children. Clinicians should consider the possibility of post-dengue Parkinsonism in children with a history of pyrexia from endemic areas of dengue. PMID:24776518

  15. Dengue fever and dengue haemorrhagic fever in adolescents and adults.

    Science.gov (United States)

    Tantawichien, Terapong

    2012-05-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients. PMID:22668446

  16. Dengue fever: theories of immunopathogenesis and challenges for vaccination.

    Science.gov (United States)

    Remy, Melissa M

    2014-01-01

    Dengue fever is a mosquito-borne viral disease infecting several hundred million people in tropical and subtropical areas every year. Its clinical manifestations range from mild fever to severe life-threatening shock syndrom. No therapeutics or licensed vaccines are available yet and with half of the world's population already at risk, it represents a major public health concern. The co-existence of four different Dengue virus serotypes renders difficult the obtaining of full protective immunity against each one of them. On the contrary, these serotypes trigger significant cross-reactivities of antibodies and T cells, both of which may lead to disease enhancement when reactivated in the context of reinfection with a heterologous serotype. Several immunological concepts have been developed to explain disease enhancement, and the uncertainty around the topic has consequently slowed down the development of Dengue vaccines. Recent advances however have shed light on key aspects of both the immunoprotective and immunopathological mechanisms. In particular the responses of specific antibodies and T cells have been a focus of many studies. These immunological players are thought to directly influence a cytokine dysbalance that eventually leads to severe disease and vascular leakage. In this review I outline current concepts and ongoing debates on the above topics. A better understanding of Dengue virus immunopathogenesis is critically needed to optimize candidate vaccines including those currently under development. In particular, the results from large-scale human efficacy trials will offer outstanding opportunities to refine correlates of protection and design even more effective vaccines. PMID:25163973

  17. Dengue viruses – an overview

    Directory of Open Access Journals (Sweden)

    Anne Tuiskunen Bäck

    2013-08-01

    Full Text Available Dengue viruses (DENVs cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF, and dengue shock syndrome (DSS are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  18. A portable approach for the surveillance of dengue virus-infected mosquitoes.

    Science.gov (United States)

    Muller, David A; Frentiu, Francesca D; Rojas, Alejandra; Moreira, Luciano A; O'Neill, Scott L; Young, Paul R

    2012-07-01

    Dengue virus is the most significant human viral pathogen spread by the bite of an infected mosquito. With no vaccine or antiviral therapy currently available, disease prevention relies largely on surveillance and mosquito control. Preventing the onset of dengue outbreaks and effective vector management would be considerably enhanced through surveillance of dengue virus prevalence in natural mosquito populations. However, current approaches to the identification of virus in field-caught mosquitoes require relatively slow and labor intensive techniques such as virus isolation or RT-PCR involving specialized facilities and personnel. A rapid and portable method for detecting dengue virus-infected mosquitoes is described. Using a hand held battery operated homogenizer and a dengue diagnostic rapid strip the viral protein NS1 was detected as a marker of dengue virus infection. This method could be performed in less than 30 min in the field, requiring no downstream processing, and is able to detect a single infected mosquito in a pool of at least 50 uninfected mosquitoes. The method described in this study allows rapid, real-time monitoring of dengue virus presence in mosquito populations and could be a useful addition to effective monitoring and vector control responses. PMID:22575689

  19. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

    Directory of Open Access Journals (Sweden)

    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  20. A review of dengue research in malaysia.

    Science.gov (United States)

    Cheah, W K; Ng, K S; Marzilawati, A R; Lum, L C S

    2014-08-01

    Dengue infection is a major cause of morbidity and mortality in Malaysia. To date, much research on dengue infection conducted in Malaysia have been published. One hundred and sixty six articles related to dengue in Malaysia were found from a search through a database dedicated to indexing all original data relevant to medicine published between the years 2000-2013. Ninety articles with clinical relevance and future research implications were selected and reviewed. These papers showed evidence of an exponential increase in the disease epidemic and a varying pattern of prevalent dengue serotypes at different times. The early febrile phase of dengue infection consist of an undifferentiated fever. Clinical suspicion and ability to identify patients at risk of severe dengue infection is important. Treatment of dengue infection involves judicious use of volume expander and supportive care. Potential future research areas are discussed to narrow our current knowledge gaps on dengue infection. PMID:25417953

  1. Dengue Virus May Bolster Zika's Attack

    Science.gov (United States)

    ... dengue fever virus may increase the severity of Zika virus, a new study says. Early stage laboratory findings ... Services, or federal policy. More Health News on: Zika Virus Recent Health News Related MedlinePlus Health Topics Dengue ...

  2. DAY 1 DIAGNOSIS OF DENGUE FEVER

    OpenAIRE

    Shyam; Sreelatha; Saswati; Raja; Tarkeshwar

    2014-01-01

    BACKGROUND: Dengue is an RNA virus of the family Flaviviridae transmitted by Aedes mosquitoes particularly Aedes aegypti. It is widely distributed throughout the tropics and subtropics and in a small proportion of cases the virus leads to life threatening complications dengue hemorrhagic fever and dengue shock syndrome. OBJECTIVES: To study the early diagnosis of Dengue on day 1 as there is no vaccine or specific antiviral treatment available. METHODS: A prospective study ...

  3. Hemophagocytic syndrome in classic dengue fever

    OpenAIRE

    Sayantan Ray1,*; Supratip Kundu; Manjari Saha; Prantar Chakrabarti

    2011-01-01

    A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnost...

  4. Dengue fever: a Wikipedia clinical review

    OpenAIRE

    Heilman, James M; Wolff, Jacob De; Beards, Graham M.; Basden, Brian J.

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treat...

  5. Dengue Fever in Perspective of Clustering Algorithms

    OpenAIRE

    Shaukat, Kamran; Masood, Nayyer; Shafaat, Ahmed Bin; Jabbar, Kamran; Shabbir, Hassan; Shabbir, Shakir

    2015-01-01

    Dengue fever is a disease which is transmitted and caused by Aedes Aegypti mosquitos. Dengue has become a serious health issue in all over the world especially in those countries who are situated in tropical or subtropical regions because rain is an important factor for growth and increase in the population of dengue transmitting mosquitos. For a long time, data mining algorithms have been used by the scientists for the diagnosis and prognosis of different diseases which includes dengue as we...

  6. Dengue fever outbreak: a clinical management experience

    International Nuclear Information System (INIS)

    To determine the frequency of dengue as a cause of fever and compare the clinical and haematological characteristics of Dengue-probable and Dengue-proven cases. All patients with age above 14 years, who were either hospitalized or treated in medical outdoor clinic due to acute febrile illness, were evaluated for clinical features of Dengue Fever (DF), Dengue haemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). Patients showing typical clinical features and haematological findings suggestive of Dengue fever (As per WHO criteria) were evaluated in detail for comparison of probable and confirmed cases of Dengue fever. All other cases of acute febrile illness, not showing clinical features or haematological abnormalities of Dengue fever, were excluded. The clinical and laboratory features were recorded on SPSS 11.0 programme and graded where required, for descriptive and statistical analysis. Out of 5200 patients with febrile illness, 107 (2%) presented with typical features of DF, 40/107 (37%) were Dengue-proven while 67/107 (63%) were Dengue-probable. Out of Dengue-proven cases, 38 were of DF and 2 were of DHF. Day 1 temperature ranged from 99-105 degreeC (mean 101 degree C). Chills and rigors were noticed in 86 (80%), myalgia in 67%, headache in 54%, pharyngitis in 35%, rash in 28%, and bleeding manifestations in 2% cases. Hepatomegaly in 1(0.5%), lymphadenopathy in 1 (0.5%) and splenomegaly in 12 (11.2%) cases. Leucopoenia (count 40 U/L in 57% cases. Frequency of clinically suspected dengue virus infection was 107 (2%), while confirmed dengue fever cases were 40 (0.8%) out of 5200 fever cases. Fever with chills and rigors, body aches, headache, myalgia, rash, haemorrhagic manifestations, platelet count, total leukocyte count, and ALT, are parameters to screen the cases of suspected dengue virus infection, the diagnosis cannot be confirmed unless supported by molecular studies or dengue specific IgM. (author)

  7. Reviewing dengue: still a neglected tropical disease?

    Directory of Open Access Journals (Sweden)

    Olaf Horstick

    2015-04-01

    Full Text Available Dengue is currently listed as a "neglected tropical disease" (NTD. But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D (2003-2013. NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a poverty related, b endemic to the tropics and subtropics, c lacking public health attention, d having poor research funding and shortcomings in R&D, e usually associated with high morbidity but low mortality, and f often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  8. Controlling Dengue with Vaccines in Thailand

    OpenAIRE

    Dennis L Chao; Halstead, Scott B.; M. Elizabeth Halloran; Longini, Ira M.

    2012-01-01

    BACKGROUND: Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently...

  9. Perbedaan Kadar Platelet Activating Factor Plasma antara Penderita Demam Berdarah Dengue dan Demam Dengue

    Directory of Open Access Journals (Sweden)

    Djatnika Setiabudi

    2013-12-01

    Full Text Available Dengue virus infection can manifest as dengue fever and, more severely, as dengue hemorrhagic fever. Their pathogenesis until now is not fully understood. One of the most favorable theories stated the presence of increasing titer of pro-inflammatory mediator in severe dengue. The aim of this study was to determine the difference of plasma platelet activating factor titer between dengue hemorrhagic fever and dengue fever patients. This observational study with cross sectional design was conducted during January–February 2013. Subjects were dengue patients, 1 to 14 years old, hospitalized at Dr. Hasan Sadikin General Hospital, Bandung District Hospital (Ujungberung, and Cimahi District Hospital (Cibabat. Dengue cases were confirmed based on nonstructural-1 antigen and/or immunoglobulin M and G rapid test. Blood samples from febrile, critical and recovery phase were drawn for the examination of platelet activating factor titer using the enzyme-linked immunosorbent assay method. There were 26 dengue cases (14 as dengue fever and 12 as dengue hemorrhagic fever. Plasma platelet activating factor titer at the critical phase was significantly higher in dengue hemorrhagic fever patients [541.45 (239.30–2,449.00] pg/mL compared to dengue fever patients [289.55 (149.50–961.50] pg/mL; p=0.007. In conclusion, plasma platelet activating factor titer at the critical phase is higher in dengue hemorrhagic fever patients than in dengue fever patients.

  10. Randomness of Dengue Outbreaks on the Equator.

    Science.gov (United States)

    Chen, Yirong; Cook, Alex R; Lim, Alisa X L

    2015-09-01

    A simple mathematical model without seasonality indicated that the apparently chaotic dengue epidemics in Singapore have characteristics similar to epidemics resulting from chance. Randomness as a sufficient condition for patterns of dengue epidemics in equatorial regions calls into question existing explanations for dengue outbreaks there.

  11. Randomness of Dengue Outbreaks on the Equator

    OpenAIRE

    Chen, YiRong; Cook, Alex R.; Lim, Alisa X.L.

    2015-01-01

    A simple mathematical model without seasonality indicated that the apparently chaotic dengue epidemics in Singapore have characteristics similar to epidemics resulting from chance. Randomness as a sufficient condition for patterns of dengue epidemics in equatorial regions calls into question existing explanations for dengue outbreaks there.

  12. Separation of effector cells mediating antibody-dependent cellular cytotoxicity (ADC) to erythrocyte targets from those mediating ADC to tumor targets.

    Science.gov (United States)

    Pollack, S B; Nelson, K; Grausz, J D

    1976-04-01

    Murine spleen cells mediate antibody-dependent cellular cytotoxicity (ADC) both to erythrocyte targets in a 51Cr release assay and to syngeneic tumor targets in a microcytotoxicity assay. The effector cells active in the two ADC assays can be separated by passage of the spleen cells through columns of Sephadex G-10 at 37 degrees C. Cells mediating ADC to sarcoma cells did not adhere to the G-10 and were recovered in the column effluent. These nonadherent cells were not cytotoxic to antibody-coated chicken red blood cells. Spleen cells which mediated ADC in a 51Cr release assay to the red cell targets adhered to G-10. Adherent effector cells could subsequently be recovered from the columns by elution with 5 X 10(-4) M EDTA. PMID:815438

  13. Preexisting Antibody-Dependent Cellular Cytotoxicity-Activating Antibody Responses Are Stable Longitudinally and Cross-reactive Responses Are Not Boosted by Recent Influenza Exposure.

    Science.gov (United States)

    Valkenburg, Sophie A; Zhang, Yanyu; Chan, Ka Y; Leung, Kathy; Wu, Joseph T; Poon, Leo L M

    2016-10-15

    Cross-reactive influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-activating antibodies are readily detected in healthy adults. However, little is known about the kinetics of these ADCC responses. We used retrospective serial blood samples from healthy donors to investigate this topic. All donors had ADCC responses against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and avian influenza A(H7N9) virus hemagglutinins (HAs) despite being seronegative for these viruses in standard hemagglutination inhibition and microneutralization serological assays. A(H1N1)pdm09 exposure did not boost ADCC responses specific for H7 HA antigens. H7 HA ADCC responses were variable longitudinally within donors, suggesting that these cross-reactive antibodies are unstable. We found no correlation between ADCC responses to the H7 HA and either influenza virus-specific immunoglobulin G1 concentration or age. PMID:27493238

  14. Dengue: an arthropod-borne disease of global importance.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Wagenaar, J.; Brandjes, D.P.; Gorp, E. van

    2004-01-01

    Dengue viruses cause a variable spectrum of disease that ranges from an undifferentiated fever to dengue fever to the potentially fatal dengue shock syndrome. Due to the increased incidence and geographical distribution of dengue in the last 50 years, dengue is becoming increasingly recognised as on

  15. High rates of inapparent dengue in older adults in Singapore.

    Science.gov (United States)

    Yap, Grace; Li, Chenny; Mutalib, Adeliza; Lai, Yee-Ling; Ng, Lee-Ching

    2013-06-01

    Although the dengue iceberg phenomenon is well known, there is a paucity of data on inapparent dengue. Results from a seroepidemiological study conducted during a dengue epidemic in 2007 in Singapore showed a seroprevalence of 65.9% and an inapparent dengue rate of 78%. Older adults (> 45 years old) had significantly higher rates of inapparent dengue infections (P < 0.05).

  16. High Rates of Inapparent Dengue in Older Adults in Singapore

    OpenAIRE

    Yap, Grace; Li, Chenny; Mutalib, Adeliza; Lai, Yee-Ling; Ng, Lee-Ching

    2013-01-01

    Although the dengue iceberg phenomenon is well known, there is a paucity of data on inapparent dengue. Results from a seroepidemiological study conducted during a dengue epidemic in 2007 in Singapore showed a seroprevalence of 65.9% and an inapparent dengue rate of 78%. Older adults (> 45 years old) had significantly higher rates of inapparent dengue infections (P < 0.05).

  17. Dengue in an elderly patient Dengue em paciente idosa

    Directory of Open Access Journals (Sweden)

    Milton Luiz Gorzoni

    2010-06-01

    Full Text Available Although elderly populations are more exposed to the risk of getting dengue, the clinical peculiarities of this disease in this age range are not well known. This report is about an 80-year-old woman with dengue complications, self-medicated with salicylate. Literature indicates a more severe clinical condition, high hospitalization rate and significant mortality. This is caused by previous infections by other serotypes of this arbovirus, presence of chronic diseases, immunosenescence and high drug consumption, especially salicylates and the like. Analyses are required in a public health perspective in order to help health professionals that care for patients with dengue in this age range.Embora cada vez mais populações idosas estejam expostas ao risco de contrair dengue, pouco se sabe sobre peculiaridades clínicas desta doença nesta faixa etária, fato este que motivou este relato sobre octogenária com dengue agravada por automedicação de salicilato. A literatura consultada aponta para quadro clínico mais grave, elevado índice de hospitalizações e mortalidade significativa. Deve-se isto a infecções prévias com outros sorotipos desta arbovirose, presença de doenças crônico degenerativas, imunosenescência e alto consumo de medicamentos, particularmente salicilatos e similares. Análises, sob a ótica da saúde pública, são necessárias para auxiliar aos profissionais de saúde que assistem pacientes com dengue nesta faixa etária

  18. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity.

    Science.gov (United States)

    Singla, Mohit; Kar, Meenakshi; Sethi, Tavpritesh; Kabra, Sushil K; Lodha, Rakesh; Chandele, Anmol; Medigeshi, Guruprasad R

    2016-03-01

    Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.

  19. Cells in Dengue Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  20. Novel concept on antiviral strategies to dengue.

    Science.gov (United States)

    Lo, Yu-Chih; Perng, Guey Chuen

    2016-06-01

    Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue. PMID:27284691

  1. Lethal Dengue Virus Infection: A Forensic Overview.

    Science.gov (United States)

    Byard, Roger W

    2016-06-01

    Dengue virus is a single-stranded RNA virus that is a member of the family Flaviviridae, genus Flavivirus. It is usually transmitted by the female Aedes aegypti mosquito. Dengue fever is a febrile illness caused by 1 of 4 serotypes of the virus, which may progress to dengue hemorrhagic fever or dengue shock syndrome. The mortality rate of untreated dengue shock syndrome is more than 20%. The reported incidence has increased 30-fold for the past 50 years with an estimated 50 to 100 million dengue infections globally each year, which includes 22,000 deaths. Because of this rapid increase in numbers, more cases will be seen in forensic mortuaries, with diagnostic problems arising from nonspecific or unusual manifestations. In this review, the clinicopathological features of dengue viral infection are evaluated. Adequate blood and tissue sampling at the time of autopsy is mandatory for successful microbiological identification and characterization. PMID:27093563

  2. Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

    Science.gov (United States)

    Limonta, D; Falcón, V; Torres, G; Capó, V; Menéndez, I; Rosario, D; Castellanos, Y; Alvarez, M; Rodríguez-Roche, R; de la Rosa, M C; Pavón, A; López, L; González, K; Guillén, G; Diaz, J; Guzmán, M G

    2012-12-01

    Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

  3. Dengue and Dengue Haemorrhagic Fever in French Polynesia-Current Situation

    OpenAIRE

    Chungue, Eliane; Laudon, Francois; Glaziou, Philippe

    1994-01-01

    All four dengue virus serotypes have occurred in French Polynesia. The first epidemic of dengue on Tahiti island of known serotype (dengue 1) occurred in 1944 as part of the Pacific-wide spread of the disease during World War II. The next outbreak of dengue took place in 1964 and was the result of the introduction of dengue 3 virus. With the increase in air travel by humans, dengue has occurred as successive epidemics, especially between 1969 and 1979 with each epidemic involving a different ...

  4. Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

    Science.gov (United States)

    Lim, Jacqueline Kyungah; Lee, Yong-Seok; Wilder-Smith, Annelies; Thiry, Georges; Mahoney, Richard; Yoon, In-Kyu

    2016-04-01

    Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction. PMID:26651238

  5. Models of dengue virus infection.

    Science.gov (United States)

    Bente, Dennis A; Rico-Hesse, Rebeca

    2006-01-01

    The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models. PMID:18087566

  6. Controlling dengue with vaccines in Thailand.

    Directory of Open Access Journals (Sweden)

    Dennis L Chao

    Full Text Available BACKGROUND: Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. METHODOLOGY/PRINCIPAL FINDINGS: We developed an individual-level (including both humans and mosquitoes, stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. CONCLUSIONS/SIGNIFICANCE: Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.

  7. Fractional Derivatives in Dengue Epidemics

    Science.gov (United States)

    Pooseh, Shakoor; Rodrigues, Helena Sofia; Torres, Delfim F. M.

    2011-09-01

    We introduce the use of fractional calculus, i.e., the use of integrals and derivatives of non-integer (arbitrary) order, in epidemiology. The proposed approach is illustrated with an outbreak of dengue disease, which is motivated by the first dengue epidemic ever recorded in the Cape Verde islands off the coast of west Africa, in 2009. Numerical simulations show that in some cases the fractional models fit better the reality when compared with the standard differential models. The classical results are obtained as particular cases by considering the order of the derivatives to take an integer value.

  8. Dengue fever complicated by hemophagocytosis.

    Science.gov (United States)

    Koshy, Maria; Mishra, Ajay Kumar; Agrawal, Bhumi; Kurup, Akhil Rajendra; Hansdak, Samuel George

    2016-01-01

    Dengue is a common acute viral febrile illness in the tropics. Although the usual presentation is that of a self-limiting illness, its complications are protean. We report a 29-year-old man who presented with an acute febrile illness and was diagnosed with dengue hemorrhagic fever. Despite appropriate supportive therapy, the patient initially improved, but subsequently had clinical deterioration. Evaluation revealed features of hemophagocytic lymphohistiocytosis. He was successfully treated with glucocorticoids and had an uneventful recovery. This case adds to the limited adult cases of virus-associated hemophagocytic syndrome in the literature and the need for prompt recognition and treatment of this rare complication. PMID:27274854

  9. Fractional derivatives in Dengue epidemics

    CERN Document Server

    Pooseh, Shakoor; Torres, Delfim F M

    2011-01-01

    We introduce the use of fractional calculus, i.e., the use of integrals and derivatives of non-integer (arbitrary) order, in epidemiology. The proposed approach is illustrated with an outbreak of dengue disease, which is motivated by the first dengue epidemic ever recorded in the Cape Verde islands off the coast of west Africa, in 2009. Numerical simulations show that in some cases the fractional models fit better the reality when compared with the standard differential models. The classical results are obtained as particular cases by considering the order of the derivatives to take an integer value.

  10. Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses

    Science.gov (United States)

    Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses B Z Z Z Z . Aside from being ... or Aedes albopictus ) can spread dengue, chikungunya, or Zika viruses. People become infected with dengue, chikungunya, or Zika ...

  11. Time series analysis of dengue incidence in Guadeloupe, French West Indies: Forecasting models using climate variables as predictors

    Directory of Open Access Journals (Sweden)

    Ruche Guy

    2011-06-01

    Full Text Available Abstract Background During the last decades, dengue viruses have spread throughout the Americas region, with an increase in the number of severe forms of dengue. The surveillance system in Guadeloupe (French West Indies is currently operational for the detection of early outbreaks of dengue. The goal of the study was to improve this surveillance system by assessing a modelling tool to predict the occurrence of dengue epidemics few months ahead and thus to help an efficient dengue control. Methods The Box-Jenkins approach allowed us to fit a Seasonal Autoregressive Integrated Moving Average (SARIMA model of dengue incidence from 2000 to 2006 using clinical suspected cases. Then, this model was used for calculating dengue incidence for the year 2007 compared with observed data, using three different approaches: 1 year-ahead, 3 months-ahead and 1 month-ahead. Finally, we assessed the impact of meteorological variables (rainfall, temperature and relative humidity on the prediction of dengue incidence and outbreaks, incorporating them in the model fitting the best. Results The 3 months-ahead approach was the most appropriate for an effective and operational public health response, and the most accurate (Root Mean Square Error, RMSE = 0.85. Relative humidity at lag-7 weeks, minimum temperature at lag-5 weeks and average temperature at lag-11 weeks were variables the most positively correlated to dengue incidence in Guadeloupe, meanwhile rainfall was not. The predictive power of SARIMA models was enhanced by the inclusion of climatic variables as external regressors to forecast the year 2007. Temperature significantly affected the model for better dengue incidence forecasting (p-value = 0.03 for minimum temperature lag-5, p-value = 0.02 for average temperature lag-11 but not humidity. Minimum temperature at lag-5 weeks was the best climatic variable for predicting dengue outbreaks (RMSE = 0.72. Conclusion Temperature improves dengue outbreaks forecasts

  12. High rate of unrecognized dengue virus infection in parts of the rainforest region of Nigeria.

    Science.gov (United States)

    Onoja, A B; Adeniji, J A; Olaleye, O D

    2016-08-01

    Outbreaks and sporadic dengue virus infections continue to occur in Africa. Several reports of dengue among travellers returning from some African countries to Europe and North America have raised concerns about the epidemiological situation in Africa. We investigated recent dengue infections in febrile patients during the rainy season in various urban centres in the rainforest region of Nigeria, West Africa. This cross-sectional study was conducted for 8 months in 2014 with study participants from Adeoyo Hospital Yemetu - Ibadan, Nigeria. Plasma were collected from 274 febrile patients residing in 11 Local Government Areas of Oyo State. IgM antibodies were determined using semi-quantitative sandwich ELISA. Data was analyzed using Chi - Square and Fisher's exact test with SPSS 16.0. An overall prevalence of 23.4% dengue virus infection was found among study participants. Highest monthly prevalence of 40% was in April and August. The monthly distribution pattern of dengue virus infection indicates efficient virus transmission. Routine diagnosis will enhance dengue virus surveillance and improve patient care in West Africa. PMID:27140859

  13. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation.

    Science.gov (United States)

    Hottz, Eugenio D; Lopes, Juliana F; Freitas, Carla; Valls-de-Souza, Rogério; Oliveira, Marcus F; Bozza, Marcelo T; Da Poian, Andrea T; Weyrich, Andrew S; Zimmerman, Guy A; Bozza, Fernando A; Bozza, Patricia T

    2013-11-14

    Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. Although thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in dengue pathogenesis has not been fully elucidated. We hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. Here we investigate interleukin (IL)-1β synthesis, processing, and secretion in platelets during dengue virus (DV) infection and potential contribution of these events to endothelial permeability during infection. We observed increased expression of IL-1β in platelets and platelet-derived microparticles from patients with dengue or after platelet exposure to DV in vitro. We demonstrated that DV infection leads to assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, activation of caspase-1, and caspase-1-dependent IL-1β secretion. Our findings also indicate that platelet-derived IL-1β is chiefly released in microparticles through mechanisms dependent on mitochondrial reactive oxygen species-triggered NLRP3 inflammasomes. Inflammasome activation and platelet shedding of IL-1β-rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DV-stimulated platelets induced enhanced permeability in vitro in an IL-1-dependent manner. Our findings provide new evidence that platelets contribute to increased vascular permeability in DV infection by inflammasome-dependent release of IL-1β.

  14. Nucleic acid (DNA) immunization as a platform for dengue vaccine development.

    Science.gov (United States)

    Porter, Kevin R; Raviprakash, Kanakatte

    2015-12-10

    Since the early 1990s, DNA immunization has been used as a platform for developing a tetravalent dengue vaccine in response to the high priority need for protecting military personnel deployed to dengue endemic regions of the world. Several approaches have been explored ranging from naked DNA immunization to the use of live virus vectors to deliver the targeted genes for expression. Pre-clinical animal studies were largely successful in generating anti-dengue cellular and humoral immune responses that were protective either completely or partially against challenge with live dengue virus. However, Phase 1 clinical evaluation of a prototype monovalent dengue 1 DNA vaccine expressing prM and E genes revealed anti-dengue T cell IFNγ responses, but poor neutralizing antibody responses. These less than optimal results are thought to be due to poor uptake and expression of the DNA vaccine plasmids. Because DNA immunization as a vaccine platform has the advantages of ease of manufacture, flexible genetic manipulation and enhanced stability, efforts continue to improve the immunogenicity of these vaccines using a variety of methods.

  15. Epidemiologic update on the dengue situation in the Western Pacific Region, 2010

    Directory of Open Access Journals (Sweden)

    Yuzo Arima

    2011-06-01

    Full Text Available Dengue is an emerging vectorborne infectious disease that is a major public health concern in the Asia Pacific region. Official dengue surveillance data for 2010 provided by the ministries of health were summarized as part of routine activities of the World Health Organization Regional Office for the Western Pacific. Based on reported data, dengue has continued to show an increasing trend in the Western Pacific Region. In 2010, countries and areas reported a total of 353 907 dengue cases, of which 1073 died, for a case fatality ratio of 0.30%. More than 1000 cases were reported each from Australia (North Queensland, Cambodia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore and Viet Nam. All of these countries, except for Australia where the dengue virus is not endemic, reported an increase in the number of reported cases in 2010 compared to 2009. The elevated number of cases reported in 2010 in some countries, such as the Philippines, is likely due to several factors, such as enhanced reporting and continued epidemic activity. However, increases in reported number of cases in other areas, such as Singapore and Malaysia, appear to indicate sustained epidemic activity in those countries. The continued epidemic dengue activity in the Region highlights the need for timely and routine regional sharing of information.

  16. Encephalitis in the clinical spectrum of dengue infection

    OpenAIRE

    Varatharaj Aravinthan

    2010-01-01

    Dengue viral infections are common worldwide. Clinical manifestations form a broad spectrum, and include uncomplicated dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Encephalopathy has been well reported and has classically been thought to result from the multisystem derangement that occurs in severe dengue infection; with liver failure, shock, and coagulopathy causing cerebral insult. However, there is increasing evidence for dengue viral neurotropism, suggesting that, in...

  17. Viral and epidemiological determinants of the invasion dynamics of novel dengue genotypes.

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    José Lourenço

    Full Text Available BACKGROUND: Dengue has become a major concern for international public health. Frequent epidemic outbreaks are believed to be driven by a complex interplay of immunological interactions between its four co-circulating serotypes and large fluctuations in mosquito densities. Viral lineage replacement events, caused for example by different levels of cross-protection or differences in viral fitness, have also been linked to a temporary change in dengue epidemiology. A major replacement event was recently described for South-East Asia where the Asian-1 genotype of dengue serotype 2 replaced the resident Asian/American type. Although this was proposed to be due to increased viral fitness in terms of enhanced human-to-mosquito transmission, no major change in dengue epidemiology could be observed. METHODS/RESULTS: Here we investigate the invasion dynamics of a novel, advantageous dengue genotype within a model system and determine the factors influencing the success and rate of fixation as well as their epidemiological consequences. We find that while viral fitness overall correlates with invasion success and competitive exclusion of the resident genotype, the epidemiological landscape plays a more significant role for successful emergence. Novel genotypes can thus face high risks of stochastic extinction despite their fitness advantage if they get introduced during episodes of high dengue prevalence, especially with respect to that particular serotype. CONCLUSION: The rarity of markers for positive selection has often been explained by strong purifying selection whereby the constraints imposed by dengue's two-host cycle are expected to result in a high rate of deleterious mutations. Our results demonstrate that even highly beneficial mutants are under severe threat of extinction, which would suggest that apart from purifying selection, stochastic effects and genetic drift beyond seasonal bottlenecks are equally important in shaping dengue's viral

  18. Is drought helping or killing dengue? Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2015-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  19. Could peak proteinuria determine whether patient with dengue fever develop dengue hemorrhagic/dengue shock syndrome? - A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Suhail Sufi M

    2011-08-01

    Full Text Available Abstract Background Worldwide there is a need to develop simple effective predictors that can distinguish whether a patient will progress from dengue fever (DF to life threatening dengue hemorrhagic (DHF or dengue shock syndrome (DSS. We explored whether proteinuria could be used as such a marker. Methods We included patients admitted to hospital with suspected dengue fever. Starting at enrollment until discharge, each patient's daily spot urine protein creatinine ratio (UPCR was measured. We classified those with confirmed dengue infection as DF or DHF (including DSS based on WHO criteria. Peak and day of onset of proteinuria was compared between both groups. Results Compared to those with DF, patients with DHF had significantly higher median peak proteinuria levels (0.56 versus 0.08 g/day; p Conclusions Peak UPCR could potentially predict DHF in patients with dengue requiring close monitoring and treatment.

  20. Bilateral panophthalmitis in dengue fever

    Directory of Open Access Journals (Sweden)

    Sangeetha Sriram

    2015-01-01

    Full Text Available We report the case of a 25-year-old male patient who presented with bilateral panophthalmitis as the initial ocular manifestation of dengue fever. The diagnosis was a little confusing as he initially presented with features suggestive of retrobulbar hemorrhage secondary to his very low platelet count, which is a common feature of dengue fever. Ophthalmic complications are usually seen in young adults who often present at the nadir of thrombocytopenia. Ocular findings may include anterior uveitis, vitritis, retinal hemorrhages, retinal vascular sheathing, yellow subretinal dots, retinal pigment epithelium (RPE mottling, foveolitis that is clinically seen as a round subretinal yellowish lesion at the fovea, retinochoroiditis, choroidal effusion, optic disc swelling, optic neuritis, neuroretinitis, and oculomotor nerve palsy. [1] There is only one reported case of unilateral endogenous panophthalmitis due to dengue fever. Hence, clinicians and ophthalmologists have to be aware of this vision-threatening complication of dengue for early recognition and prompt treatment to save the vision of these young patients and prevent morbidity.

  1. Dengue Virus Serotype 2 from a Sylvatic Lineage Isolated from a Patient with Dengue Hemorrhagic Fever

    OpenAIRE

    Jane Cardosa; Mong How Ooi; Phaik Hooi Tio; David Perera; Edward C Holmes; Khatijar Bibi; Zahara Abdul Manap

    2009-01-01

    Author Summary Dengue viruses are mosquito-borne RNA viruses that cause a spectrum of illness from mild disease to life-threatening dengue hemorrhagic fever (DHF). Dengue viruses exist in two separate cycles in nature, circulating in either non-human primates or humans. The viruses that are endemic in humans today most likely evolved from non-human primate dengue viruses a few hundred years ago and have since established themselves as four distinct serotypes in human populations, causing peri...

  2. DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue

    OpenAIRE

    Wang, QuanQiu; Xu, Rong

    2015-01-01

    Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algori...

  3. Penentuan Serotipe Virus Dengue dan Gambaran Manifestasi Klinis serta Hematologi Rutin pada Infeksi Virus Dengue

    OpenAIRE

    Basti Andriyoko; Ida Parwati; Anna Tjandrawati; Leni Lismayanti

    2012-01-01

    All DENV serotypes can cause a spectrum of disease from dengue fever (DF) to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). It is difficult to differentiate clinical characteristicand hematologic result for each serotype. Aim of this study were to determine dengue serotype and describe clinical manifestation of DF, DHF, DSS and routine hematologic results, i.e.haemoglobin, hematocrit, leukocyte, and thrombocyte in each serotype. This study was conducted at Dr. Hasan Sadikin H...

  4. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B; Russell, Philip K

    2016-03-29

    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed.

  5. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B; Russell, Philip K

    2016-03-29

    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. PMID:26873054

  6. Relationship between Breteau and House indices and cases of dengue/dengue hemorrhagic fever in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Sulaiman, S; Pawanchee, Z A; Arifin, Z; Wahab, A

    1996-09-01

    The relationship between the Breteau index, the House index, and the occurrence of dengue/dengue hemorrhagic fever in the 6 zones of Kuala Lumpur was studied throughout 1994. Cases of dengue/dengue hemorrhagic fever varied between zones and between months, ranging from 0 to 21 cases. In most of the zones in Kuala Lumpur, the occurrence of dengue/dengue hemorrhagic fever has no relationship with the Breteau and House indices. Cases of dengue/dengue hemorrhagic fever occurred in all zones despite the low Breteau and House indices.

  7. DAY 1 DIAGNOSIS OF DENGUE FEVER

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    Shyam

    2014-09-01

    Full Text Available BACKGROUND: Dengue is an RNA virus of the family Flaviviridae transmitted by Aedes mosquitoes particularly Aedes aegypti. It is widely distributed throughout the tropics and subtropics and in a small proportion of cases the virus leads to life threatening complications dengue hemorrhagic fever and dengue shock syndrome. OBJECTIVES: To study the early diagnosis of Dengue on day 1 as there is no vaccine or specific antiviral treatment available. METHODS: A prospective study of 104 patients was done based on clinical criteria of Dengue. RESULTS: Out of 104 serum samples 46 (44% were positive by NSI Ag MICROELISA, 37 (35% by NSI antigen IMMUNO CHROMATOGRAPHY. 3 (2% samples are positive by IgM IMMUNO CHROMATOGRAPHY and only one sample was positive for IgG IMMUNOCHROMATOGRAPHY. CONCLUSION: The present study has established the significance of NSI Ag MICROELISA with NSI antigen IMMUNO CHROMATOGRAPHY in increasing the diagnostic efficiency in the day 1 diagnosis of Dengue fever.

  8. Hemophagocytic syndrome in classic dengue fever

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    Sayantan Ray

    2011-01-01

    Full Text Available A 24-year-old previously healthy girl presented with persistent fever, headache, and jaundice. Rapid-test anti-dengue virus IgM antibody was positive but anti-dengue IgG was nonreactive, which is suggestive of primary dengue infection. There was clinical deterioration during empiric antibiotic and symptomatic therapy. Bone marrow examination demonstrated the presence of hemophagocytosis. Diagnosis of dengue fever with virus-associated hemophagocytic syndrome was made according to the diagnostic criteria of the HLH 2004 protocol of the Histiocyte Society. The patient recovered with corticosteroid therapy. A review of literature revealed only a handful of case reports that showed the evidence that this syndrome is caused by dengue virus. Our patient is an interesting case of hemophagocytic syndrome associated with classic dengue fever and contributes an additional case to the existing literature on this topic. This case highlights the need for increased awareness even in infections not typically associated with hemophagocytic syndrome.

  9. Dengue myocarditis in Singapore: two case reports.

    Science.gov (United States)

    Marques, N; Gan, V C; Leo, Y-S

    2013-06-01

    The authors report two cases of complicated dengue viral infection with acute myocarditis involving young male adults, of which one was fatal. The first case presented with typical signs of myocardial disease: chest pain and diaphoresis with myocardial depression in the electrocardiograph. The second case deteriorated rapidly and demised within the first day of admission. Histology of the heart muscles showed multiple small foci of myocyte necrosis surrounded by lymphocytes, in keeping with viral myocarditis. Both cases fulfilled the World Health Organization (WHO) diagnosis of probable dengue: the first case had positive dengue serology, both IgM and IgG at day six of illness, and the second case was polymerase chain reaction (PCR) positive for dengue and identified as serotype 2. Despite the severe outcome, both cases did not completely fulfil the criteria for dengue haemorrhagic fever (DHF). Although severe cardiac impairment is not commonly reported in dengue infection, it can be life threatening.

  10. A dengue model incorporating saturation incidence and human migration

    Science.gov (United States)

    Gakkhar, S.; Mishra, A.

    2015-03-01

    In this paper, a non-linear model has been proposed to investigate the effects of human migration on dengue dynamics. Human migration has been considered between two patches having different dengue strains. Due to migration secondary infection is possible. Further, the secondary infection is considered in patch-2 only as strain-2 in patch-2 is considered to be more severe than that of strain-1 in patch-1. The saturation incidence rate has been considered to incorporate the behavioral changes towards epidemic in human population. The basic reproduction number has been computed. Four Equilibrium states have been found and analyzed. Increasing saturation rate decreases the threshold thereby enhancing the stability of disease-free state in both the patches. Control on migration may lead to change in infection level of patches.

  11. Neurological manifestations of dengue viral infection

    OpenAIRE

    Carod-Artal FJ

    2014-01-01

    Francisco Javier Carod-Artal1,21Neurology Department, Raigmore hospital, Inverness, UK; 2Universitat Internacional de Catalunya (UIC), Barcelona, Spain Abstract: Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%–7.4% of symptomatic cases. Neurological complications have been classified into de...

  12. KNOWLEDGE OF MEDICAL PROFESSIONALS TOWARDS DENGUE DIAGNOSTICS

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    Saranya Selvanayaki

    2016-06-01

    Full Text Available Dengue is a major public health problem throughout the world. It is a rapidly spreading mosquito-borne viral disease with high rate of morbidity and mortality. Dengue can be reduced by implementing early case detection, reorienting health services, improving outbreak prediction and detection through coordinated epidemic and appropriate vector management. Various diagnostic techniques like ELISA, Rapid tests, etc. are very useful in diagnosis of dengue. Diagnosis of dengue is the most essential step to curb any mass outbreak of the disease. OBJECTIVES The objectives of the study were to find the existing knowledge of Dengue among medical professionals and preference of diagnostic techniques of dengue and to elicit acceptability and affordability of such measures and to highlight the policies regarding dengue diagnostics. METHOD A questionnaire survey was conducted among 100 doctors using a pretested open-ended questionnaire. The result was analysed and interpreted. RESULTS The knowledge of medical professionals regarding the preference of dengue diagnostics varies; 56% of the medical professionals prefer IgM antibody ELISA test, 41% prefer NS I antigen test and only 3% prefer RT – PCR; 100% of the medical professionals agreed that platelet count decreases during the course of infection. An increase of haematocrit value was thought to be important by 73% professionals. Interestingly, 20% of the medical professionals reported that no change in haematocrit value and 7% reported that haematocrit value would decrease. The knowledge of availability of ELISA was 72%. However, 83% of medical professionals agreed that IgM antibody ELISA test was a rapid test for Dengue diagnosis. CONCLUSION Laboratory infrastructure, technical expertise and research capacity must be improved in order to positively influence dengue surveillance, clinical case management and development of new approaches to dengue control. CME on dengue is suggested to improve the

  13. Sensorineural hearing loss in hemorrhagic dengue?

    OpenAIRE

    Bruna Natália Freire Ribeiro; Alexandre Caixeta Guimarães; Felipe Yazawa; Tammy Fumiko Messias Takara; Guilherme Machado de Carvalho; Carlos Eduardo Monteiro Zappelini

    2014-01-01

    Introduction: Dengue is an acute febrile infectious disease, with high fever followed by symptoms flu-like. Dengue hemorrhagic fever (DHF) is a vascular leak syndrome and could present spontaneous bleeding and worsening of symptoms after some days. Dengue could have some ENT manifestations, however hearing loss is not one of them. Sudden hearing loss is considered as sensorineural or perceptual hearing loss with a sudden onset in a person without other prior otological history. The relation b...

  14. Cross-Reactive T-Cell Responses to the Nonstructural Regions of Dengue Viruses among Dengue Fever and Dengue Hemorrhagic Fever Patients in Malaysia▿

    OpenAIRE

    Appanna, Ramapraba; Huat, Tan Lian; See, Lucy Lum Chai; Tan, Phoay Lay; Vadivelu, Jamuna; Devi, Shamala

    2007-01-01

    Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue ...

  15. n Silico Analysis of Envelope Dengue Virus-2 and Envelope Dengue Virus-3 Protein as the Backbone of Dengue Virus Tetravalent Vaccine by Using Homology Modeling Method

    OpenAIRE

    Rizky I. Taufik; Hendra; Parikesit, Arli A; Usman S.F. Tambunan; Fitri Amelia; Syamsudin

    2009-01-01

    Problem statement: Dengue fever, which was caused by Dengue virus infection, had became a major public health problem in the tropic and subtropical countries. Dengue virus (DENV) had four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4), based on their immunogenic in the human body. Preventive measure will be necessary to decrease the prevalence of dengue fever, by developing modern vaccine. Approach: This research was focused on in silico study of dengue viru...

  16. Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.

    Science.gov (United States)

    Scott, Lesley J

    2016-09-01

    Tetravalent, live-attenuated, dengue vaccine (Dengvaxia(®); CYD-TDV) is the first vaccine approved for the prevention of dengue disease caused by dengue virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high dengue endemic areas. This narrative review discusses the immunogenicity, protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of dengue disease. In Latin American and Asian phase 3 trials in children and adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was efficacious in preventing virologically-confirmed dengue (VCD) during the period from 28 days after the last dose (month 13) to month 25, meeting the primary endpoint criteria. Protective efficacy against VCD in the respective individual trials was 60.8 and 56.5 % (primary analysis). During the 25-month active surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in children aged 9 years and older. CYD-TDV was generally well tolerated, with no safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1) in ongoing long-term studies. Based on evidence from the dengue clinical trial program, the WHO SAGE recommended that countries with high dengue endemicity consider introducing CYD-TDV as part of an integrated disease prevention strategy to lower disease burden. Pharmacoeconomic considerations will be pivotal to implementing dengue vaccination prevention strategies in these countries. The availability of a dengue vaccine is considered essential if the 2012 WHO global strategy targets for reducing the burden of dengue disease by 2020 are to be attained. Hence, CYD-TDV represents a major advance for the prevention of dengue disease in high dengue endemic regions. PMID:27506852

  17. An Unusual Ocular Emergency in Severe Dengue

    Science.gov (United States)

    Nagaraj, Kalpana Badami; Jayadev, Chaitra; Yajmaan, Soumya; Prakash, Savitha

    2014-01-01

    Dengue, one of the most common mosquito-borne flavivirus diseases affecting humans, is spread by the Aedes aegypti mosquito. Most people infected with dengue virus are asymptomatic or only have mild symptoms such as an uncomplicated fever; few have more severe features, while in a small proportion it is life-threatening. Severe dengue is defined as that associated with severe bleeding, severe organ dysfunction, or severe plasma leakage. Ophthalmic manifestations can involve both the anterior and posterior segment. We report an ocular emergency of proptosis and globe rupture in a patient with severe dengue. PMID:25371643

  18. Chloroquine use improves dengue-related symptoms

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    Marcos Carvalho Borges

    2013-08-01

    Full Text Available Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63% with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004 while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.

  19. An unusual ocular emergency in severe dengue

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    Kalpana Badami Nagaraj

    2014-01-01

    Full Text Available Dengue, one of the most common mosquito-borne flavivirus diseases affecting humans, is spread by the Aedes aegypti mosquito. Most people infected with dengue virus are asymptomatic or only have mild symptoms such as an uncomplicated fever; few have more severe features, while in a small proportion it is life-threatening. Severe dengue is defined as that associated with severe bleeding, severe organ dysfunction, or severe plasma leakage. Ophthalmic manifestations can involve both the anterior and posterior segment. We report an ocular emergency of proptosis and globe rupture in a patient with severe dengue.

  20. Challenges in dengue surveillance and control

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    Lee Ching Ng

    2011-04-01

    Full Text Available Globally, the challenge posed by dengue has escalated at an astonishing rate in the last three decades, with no sign of abating. It is estimated that dengue affects at least 50 million – 100 million people every year. With more than 120 dengue-endemic countries, 3.6 billion people are at risk of infection. More than 70% of those at risk reside in the Asia Pacific region, making this region an epicentre of dengue activity.In addition to making a comeback in places such as the Americas and Singapore, where dengue was previously successfully controlled for decades, the virus has also breached the subtropical-temperate barrier as it claims new territories. In the last decade, dengue transmission has extended its reach into places as far north as Nepal, Ningbo in China and France, and as far south as Bueno Aires in Argentina. The Pacific islands, with much lower population densities, have also not been spared, with increasing dengue outbreaks since the 1970s.The direct economic and social impact of dengue on dengue-endemic regions is high,9–12 and the burden in other aspects such as the security of blood supplies is increasingly being recognized. Dengue’s threat to travellers has also been systematically demonstrated by a 2008 study on 6957 travellers who returned ill and sought treatment from EuroTravNet centres. Of those travellers, 1.9% were diagnosed with dengue, and one of the three deaths reported was due to dengue shock syndrome.

  1. Spatio-temporal modelling of climate-sensitive disease risk: Towards an early warning system for dengue in Brazil

    Science.gov (United States)

    Lowe, Rachel; Bailey, Trevor C.; Stephenson, David B.; Graham, Richard J.; Coelho, Caio A. S.; Sá Carvalho, Marilia; Barcellos, Christovam

    2011-03-01

    This paper considers the potential for using seasonal climate forecasts in developing an early warning system for dengue fever epidemics in Brazil. In the first instance, a generalised linear model (GLM) is used to select climate and other covariates which are both readily available and prove significant in prediction of confirmed monthly dengue cases based on data collected across the whole of Brazil for the period January 2001 to December 2008 at the microregion level (typically consisting of one large city and several smaller municipalities). The covariates explored include temperature and precipitation data on a 2.5°×2.5° longitude-latitude grid with time lags relevant to dengue transmission, an El Niño Southern Oscillation index and other relevant socio-economic and environmental variables. A negative binomial model formulation is adopted in this model selection to allow for extra-Poisson variation (overdispersion) in the observed dengue counts caused by unknown/unobserved confounding factors and possible correlations in these effects in both time and space. Subsequently, the selected global model is refined in the context of the South East region of Brazil, where dengue predominates, by reverting to a Poisson framework and explicitly modelling the overdispersion through a combination of unstructured and spatio-temporal structured random effects. The resulting spatio-temporal hierarchical model (or GLMM—generalised linear mixed model) is implemented via a Bayesian framework using Markov Chain Monte Carlo (MCMC). Dengue predictions are found to be enhanced both spatially and temporally when using the GLMM and the Bayesian framework allows posterior predictive distributions for dengue cases to be derived, which can be useful for developing a dengue alert system. Using this model, we conclude that seasonal climate forecasts could have potential value in helping to predict dengue incidence months in advance of an epidemic in South East Brazil.

  2. Epidemiology of Infant Dengue Cases Illuminates Serotype-Specificity in the Interaction between Immunity and Disease, and Changes in Transmission Dynamics.

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    Hannah Clapham

    2015-12-01

    Full Text Available Infants born to dengue immune mothers acquire maternal antibodies to dengue. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. Infants have long been studied to understand the interaction between infection and disease on an individual level.Considering infants (cases <1 year old as a unique group, we analyzed serotype specific dengue case data from patients admitted to a pediatric hospital in Bangkok, Thailand. We show differences in the propensity of serotypes to cause disease in individuals with dengue antibodies (infants and post-primary cases and in individuals without dengue antibodies (primary cases. The mean age of infant cases differed among serotypes, consistent with previously observed differential waning of maternal antibody titers by serotype. We show that trends over time in epidemiology of infant cases are consistent with those observed in the whole population, and therefore with trends in the force of infection.Infants with dengue are informative about the interaction between antibody and the dengue serotypes, confirming that in this population DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody despite infections occurring in others. We also observe differences between the serotypes in the mean age in infant cases, informative about the interaction between waning immunity and disease for the different serotypes in infants. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.

  3. Dengue virus and dengue fever%登革病毒和登革热

    Institute of Scientific and Technical Information of China (English)

    崔晓云; 吴艳花; 安静

    2014-01-01

    Dengue fever(DF) is the most widespread mosquito-borne diseases worldwide, caused by Dengue virus(DV). There are nearly half of the world's populations at the risk of infection in tropical and subtropical countries. DF is divided into Dengue and severe Dengue, which include Dengue hemorrhagic fever(DHF) and Dengue shock syndrome(DSS). With an estimated 500 000 cases of life-threatening disease in the form of severe Dengue every year, most of them are children. Notably, there is the most serious DF outbreak in southern China at 2014. This review will summarize several aspects of Dengue virus and Dengue fever to provide the information to the colleagues.%登革热(Dengue fever,DF)是由登革病毒(Dengue virus,DV)引起的一种虫媒传染病,主要在热带亚热带地区流行,全世界将近一半的人口有罹患 DF 的风险。 DF 在临床上分为 DF 和重症登革( severe Dengue),后者包括登革出血热( Dengue hemorrhagic fever,DHF)和登革休克综合征(Dengue shock syndrome,DSS)。每年重症登革病例达500000例,其中大多数患者为儿童。2014年 DF 在我国的南方地区出现历史上最严重的疫情,对人类健康和社会经济造成了严重损失。为此,本文对 DV 和DF 的概况作一综述,供广大同行参考。

  4. Wolbachia versus dengue: Evolutionary forecasts.

    Science.gov (United States)

    Bull, James J; Turelli, Michael

    2013-01-01

    A novel form of biological control is being applied to the dengue virus. The agent is the maternally transmitted bacterium Wolbachia, naturally absent from the main dengue vector, the mosquito Aedes aegypti. Three Wolbachia-based control strategies have been proposed. One is suppression of mosquito populations by large-scale releases of males incompatible with native females; this intervention requires ongoing releases. The other interventions transform wild mosquito populations with Wolbachia that spread via the frequency-dependent fitness advantage of Wolbachia-infected females; those interventions potentially require just a single, local release for area-wide disease control. One of these latter strategies uses Wolbachia that shortens mosquito life, indirectly preventing viral maturation/transmission. The other strategy uses Wolbachia that block viral transmission. All interventions can be undermined by viral, bacterial or mosquito evolution; viral virulence in humans may also evolve. We examine existing theory, experiments and comparative evidence to motivate predictions about evolutionary outcomes. (i) The life-shortening strategy seems the most likely to be thwarted by evolution. (ii) Mosquito suppression has a reasonable chance of working locally, at least in the short term, but long-term success over large areas is challenging. (iii) Dengue blocking faces strong selection for viral resistance but may well persist indefinitely at some level. Virulence evolution is not mathematically predictable, but comparative data provide no precedent for Wolbachia increasing dengue virulence. On balance, our analysis suggests that the considerable possible benefits of these technologies outweigh the known negatives, but the actual risk is largely unknown. PMID:24481199

  5. High concentrations of therapeutic IgG1 antibodies are needed to compensate for inhibition of antibody-dependent cellular cytotoxicity by excess endogenous immunoglobulin G.

    Science.gov (United States)

    Preithner, Susanne; Elm, Stefanie; Lippold, Sandra; Locher, Mathias; Wolf, Andreas; da Silva, Antonio J; Baeuerle, Patrick A; Prang, Nadja S

    2006-03-01

    A common feature of human IgG1 antibodies used for cancer treatment is that their anti-tumour efficacy requires high serum trough levels and continued therapy for several months. Treatment cycles, thereby, consume several grams of IgG1 translating into significant drug needs and costs. The basis for the low in vivo efficacy, which is in contrast to high in vitro antibody-dependent cellular cytotoxicity (ADCC), is not well understood. Here, we have explored factors contributing to this discrepancy using adecatumumab (MT201), a fully human monoclonal IgG1 against epithelial cell adhesion molecule (Ep-CAM) and trastuzumab (Herceptin), a humanized IgG1 with specificity for the human epithelial growth factor receptor type 2 (HER-2) antigen. We found that physiological levels of human sera strongly inhibited ADCC of both IgG1 antibodies. Effects showed some dependence on the density of Ep-CAM and HER-2 targets, the tumour cell line tested and on effector cell and serum donors. Removal of IgG by affinity chromatography abolished the inhibitory effect of a serum pool. Inhibition of ADCC was fully restored by adding back the IgG fraction or by an equal amount of IgG from a commercial source. We further demonstrate that CD56-positive lymphocytes within human PBMC contributed >90% to ADCC and that normal serum levels of IgG effectively competed for in vitro binding of an IgG1 antibody to low-affinity Fcgamma receptor type III (CD16), as is present on natural killer (NK) cells. Competition of serum IgG for binding of therapeutic IgG1 to NK cell may be one important reason why high antibody doses are required in the clinic for treatment of cancer by an ADCC-based mechanism. PMID:16102830

  6. Long-term preservation of antibody-dependent cellular cytotoxicity (ADCC) of natural killer cells amplified in vitro from the peripheral blood of breast cancer patients after chemotherapy.

    Science.gov (United States)

    Clémenceau, Béatrice; Gallot, Géraldine; Vivien, Régine; Gaschet, Joëlle; Campone, Mario; Vié, Henri

    2006-01-01

    Twenty percent of breast cancer adenocarcinomas overexpress the oncogene c-erb-2 that is recognized by the humanized anti-Her2/neu monoclonal antibody Herceptin. Results from clinical studies suggest that antibody-dependent cellular cytotoxicity (ADCC) is involved in the clinical response of Herceptin-treated patients. The purpose of the current study was to evaluate the possibility of amplifying in vitro the CD3-/CD16+ natural killer (NK) cell subset that mediates ADCC from breast cancer patients after chemotherapy. Peripheral blood mononuclear cells from six breast cancer patients taken 2 months after chemotherapy completion were co-cultured with an autologous irradiated Epstein-Barr virus-transformed B-lymphoblastoid cell line (LCL) in the presence of interleukin-2 (IL-2) for 4-6 weeks. These LCL + IL2 activated cultures (ACs) were tested for ADCC potential, and their CD3/CD16 NK proportion was quantified. Among the ACs, the proportion of CD3-/CD16+ NK cells increased up to 64% over the first 2 weeks of culture and the ACs continued to expand for 1 month thereafter. Control and patient ACs displayed ADCC activity (tested in the presence of Rituximab against the autologous LCL to take into account any possible effect of inhibitory NK receptors) as well as against the MCF-7(Her2/neu) breast cancer cell line in the presence of Herceptin. This ADCC activity was maintained during the entire culture period. In conclusion, chemotherapy in breast cancer patients does not obviate the possibility of amplifying in vitro the NK cell subset that mediates ADCC. Consequently, adoptive transfer of lymphocytes mediating ADCC can be considered using this protocol to test its benefit in patients under Herceptin treatment. PMID:16365600

  7. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.

    Science.gov (United States)

    Bonsignori, Mattia; Pollara, Justin; Moody, M Anthony; Alpert, Michael D; Chen, Xi; Hwang, Kwan-Ki; Gilbert, Peter B; Huang, Ying; Gurley, Thaddeus C; Kozink, Daniel M; Marshall, Dawn J; Whitesides, John F; Tsao, Chun-Yen; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Kim, Jerome H; Michael, Nelson L; Tomaras, Georgia D; Montefiori, David C; Lewis, George K; DeVico, Anthony; Evans, David T; Ferrari, Guido; Liao, Hua-Xin; Haynes, Barton F

    2012-11-01

    The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs. PMID:22896626

  8. Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

    Science.gov (United States)

    Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S

    2016-09-01

    Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

  9. Re-emergence of dengue virus serotype 2 strains in the 2013 outbreak in Nepal

    Directory of Open Access Journals (Sweden)

    Birendra Prasad Gupta

    2015-01-01

    Full Text Available Background & objectives: Epidemiological interventions and mosquito control are the available measures for dengue control. The former approach uses serotype and genetic information on the circulating virus strains. Dengue has been frequently reported from Nepal, but this information is mostly lacking. The present study was done to generate a comprehensive clinical and virological picture of a dengue outbreak in Nepal during 2013. Methods: A hospital-based study involving patients from five districts of Nepal was carried out. Demographic information, clinical details and dengue serological status were obtained. Viral RNA was characterized at the molecular level by reverse-transcription polymerase chain reaction (RT-PCR, nucleotide sequencing and phylogenetic analysis. Results: From among the 2340 laboratory-confirmed dengue cases during the study period, 198 patients consented for the study. Clinically they had fever (100%, headache (59.1%, rashes (18.2%, retro-orbital pain (30.3%, vomiting (15.1%, joint pain (28.8% and thrombocytopenia (74.3%. Fifteen (7.5% of them had mucosal bleeding manifestations, and the rest were uncomplicated dengue fever. The patients were mostly adults with a mean age of 45.75 ± 38.61 yr. Of the 52 acute serum samples tested, 15 were positive in RT-PCR. The causative virus was identified as DENV serotype 2 belonging to the Cosmopolitan genotype. Interpretations & conclusions: We report here the involvement of DENV serotype 2 in an outbreak in Nepal in 2013. Earlier outbreaks in the region in 2010 were attributed to serotype 1 virus. As serotype shifts are frequently associated with secondary infections and severe disease, there is a need for enhancing surveillance especially in the monsoon and post-monsoon periods to prevent large-scale, severe dengue outbreaks in the region.

  10. Recent Advances in Dengue: Relevance to Puerto Rico.

    Science.gov (United States)

    Noyd, David H; Sharp, Tyler M

    2015-06-01

    Dengue represents an increasingly important public health challenge in Puerto Rico, with recent epidemics in 2007, 2010, and 2012-2013. Although recent advances in dengue vaccine development offer hope for primary prevention, the role of health professionals in the diagnosis and management of dengue patients is paramount. Case definitions for dengue, dengue with warning signs, and severe dengue provide a framework to guide clinical decision-making. Furthermore, the differentiation between dengue and other acute febrile illnesses, such as leptospirosis and chikungunya, is necessary for the appropriate diagnosis and management of cases. An understanding of dengue epidemiology and surveillance in Puerto Rico provides context for clinicians in epidemic and non-epidemic periods. This review aims to improve health professionals' ability to diagnose dengue, and as highlight the relevance of recent advances in dengue prevention and management in Puerto Rico.

  11. Dengue and Chikungunya Vector Control Pocket Guide

    Science.gov (United States)

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  12. Atypical respiratory complications of dengue fever

    Institute of Scientific and Technical Information of China (English)

    Naveen Kumar; AK Gadpayle; Deepshikha Trisal

    2013-01-01

    In last decade, dengue has emerged as one of the most important vector born disease.With increasing cases, uncommon presentations and complications are now commonly recognized. Here, we report two cases of rare pattern of respiratory involvement in dengue: acute respiratory distress syndrome and bronchiolitis with respiratory failure.

  13. Social justice, climate change, and dengue.

    Science.gov (United States)

    Chang, Aileen Y; Fuller, Douglas O; Carrasquillo, Olveen; Beier, John C

    2014-06-14

    Climate change should be viewed fundamentally as an issue of global justice. Understanding the complex interplay of climatic and socioeconomic trends is imperative to protect human health and lessen the burden of diseases such as dengue fever. Dengue fever is rapidly expanding globally. Temperature, rainfall, and frequency of natural disasters, as well as non-climatic trends involving population growth and migration, urbanization, and international trade and travel, are expected to increase the prevalence of mosquito breeding sites, mosquito survival, the speed of mosquito reproduction, the speed of viral incubation, the distribution of dengue virus and its vectors, human migration patterns towards urban areas, and displacement after natural disasters. The burden of dengue disproportionately affects the poor due to increased environmental risk and decreased health care. Mobilization of social institutions is needed to improve the structural inequalities of poverty that predispose the poor to increased dengue fever infection and worse outcomes. This paper reviews the link between dengue and climatic factors as a starting point to developing a comprehensive understanding of how climate change affects dengue risk and how institutions can address the issues of social justice and dengue outbreaks that increasingly affect vulnerable urban populations.

  14. Dengue fever with unusual thalamic involvement.

    Science.gov (United States)

    Mallick, Asim Kumar; Purkait, Radheshyam; Sinhamahapatra, Tapan Kumar

    2012-01-01

    Dengue is the most important mosquito-borne viral disease in the world and is caused by four distinct viruses (type 1 to 4) that are closely related antigenically. Infection by dengue virus may be asymptomatic or may lead to undifferentiated fever, dengue fever or dengue haemorrhagic fever. Recent observations indicate that the clinical profile of dengue is changing and the neurological complications are being reported more frequently. The neurological features includeheadache, seizures, neck stiffness, depressed sensorium, behavioural disorders, delirium, paralysis and cranial nerve palsies. Such neurological symptoms in dengue fever wereattributed to cerebral oedema, haemorrhage, haemoconcentration due to increasing vascular permeability, coagulopathy and release of toxic substances. Cerebral oedema, encephalitis-like changes (oedema and scattered focal lesions), intracranial haemorrhages as well as selective involvement of bilateral hippocampus in dengue infection have been reported previously on selective neuro-imaging but thalamic involvement is rare. We here report a case of a typical presentation of encephalopathy with left sided complete hemiplegia due to thalamic involvement in dengue infection.

  15. Prevalence of Dengue Infection in India

    Directory of Open Access Journals (Sweden)

    G. Pandya

    1982-10-01

    Full Text Available Infections attributable to dengue viruses have been frequently occurring in India, as also in South East Asian countries. Benign clinical manifestations, have been rampant in this country. Various aspects of dengue infections in the context of India e.g., occurrence, clinical profile, viral isolations, serological surveys, pathogenicity and vector ecology have been discussed in the present review.

  16. Social justice, climate change, and dengue.

    Science.gov (United States)

    Chang, Aileen Y; Fuller, Douglas O; Carrasquillo, Olveen; Beier, John C

    2014-01-01

    Climate change should be viewed fundamentally as an issue of global justice. Understanding the complex interplay of climatic and socioeconomic trends is imperative to protect human health and lessen the burden of diseases such as dengue fever. Dengue fever is rapidly expanding globally. Temperature, rainfall, and frequency of natural disasters, as well as non-climatic trends involving population growth and migration, urbanization, and international trade and travel, are expected to increase the prevalence of mosquito breeding sites, mosquito survival, the speed of mosquito reproduction, the speed of viral incubation, the distribution of dengue virus and its vectors, human migration patterns towards urban areas, and displacement after natural disasters. The burden of dengue disproportionately affects the poor due to increased environmental risk and decreased health care. Mobilization of social institutions is needed to improve the structural inequalities of poverty that predispose the poor to increased dengue fever infection and worse outcomes. This paper reviews the link between dengue and climatic factors as a starting point to developing a comprehensive understanding of how climate change affects dengue risk and how institutions can address the issues of social justice and dengue outbreaks that increasingly affect vulnerable urban populations. PMID:25474614

  17. Dengue hemorrhagic fever complicated by pancreatitis

    OpenAIRE

    Guido Ricardo Gonzalez Fontal; Andres Felipe Henao-Martinez

    2011-01-01

    Acute pancreatitis is an atypical complication of dengue fever and is rarely described. We are reporting a case of dengue hemorrhagic fever complicated by acute pancreatitis in a patient with history of diabetes mellitus type 1 and end stage renal disease on hemodialysis.

  18. Dengue hemorrhagic fever complicated by pancreatitis

    Directory of Open Access Journals (Sweden)

    Guido Ricardo Gonzalez Fontal

    2011-10-01

    Full Text Available Acute pancreatitis is an atypical complication of dengue fever and is rarely described. We are reporting a case of dengue hemorrhagic fever complicated by acute pancreatitis in a patient with history of diabetes mellitus type 1 and end stage renal disease on hemodialysis.

  19. Vector biology prospects in dengue research

    Directory of Open Access Journals (Sweden)

    Louis Lambrechts

    2012-12-01

    Full Text Available We argue that using more natural blood feeding methods to study mosquito vector competence for dengue viruses and exploring the effect of viral infection on other mosquito life-history traits that influence vectorial capacity will significantly advance our understanding of dengue epidemiology.

  20. Vector biology prospects in dengue research

    OpenAIRE

    Louis Lambrechts; Anna-Bella Failloux

    2012-01-01

    We argue that using more natural blood feeding methods to study mosquito vector competence for dengue viruses and exploring the effect of viral infection on other mosquito life-history traits that influence vectorial capacity will significantly advance our understanding of dengue epidemiology.

  1. Protect Yourself and Your Baby from Dengue

    Science.gov (United States)

    ... at http://npic.orst.edu/ General information about dengue, contact the Centers for Disease Control and Prevention (CDC) at: 1-800-232-4636 or at http://www.cdc.gov/dengue/ CS216552 National Center for Emerging and Zoonotic Infectious ...

  2. [Hepatic alterations in patients with dengue].

    Science.gov (United States)

    Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

    2005-06-01

    Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

  3. Transmission spectroscopy of dengue viral infection

    International Nuclear Information System (INIS)

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 – 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 – 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 – 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients

  4. Real-time forecasts of dengue epidemics

    Science.gov (United States)

    Yamana, T. K.; Shaman, J. L.

    2015-12-01

    Dengue is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas with endemic dengue, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission is a significant public health challenge. Here we present a model of dengue transmission and a framework for optimizing model simulations with real-time observational data of dengue cases and environmental variables in order to generate ensemble-based forecasts of the timing and severity of disease outbreaks. The model-inference system is validated using synthetic data and dengue outbreak records. Retrospective forecasts are generated for a number of locations and the accuracy of these forecasts is quantified.

  5. Dissecting Japan's Dengue Outbreak in 2014.

    Science.gov (United States)

    Quam, Mikkel B; Sessions, October; Kamaraj, Uma Sangumathi; Rocklöv, Joacim; Wilder-Smith, Annelies

    2016-02-01

    Despite Japan's temperate climate, a dengue outbreak occurred in Tokyo for the first time in over 70 years in 2014. We dissected this dengue outbreak based on phylogenetic analysis, travel interconnectivity, and environmental drivers for dengue epidemics. Comparing the available dengue virus 1 (DENV1) E gene sequence from this outbreak with 3,282 unique DENV1 sequences in National Center for Biotechnology Information suggested that the DENV might have been imported from China, Indonesia, Singapore, or Vietnam. With travelers arriving into Japan, Guangzhou (China) may have been the source of DENV introduction, given that Guangzhou also reported a large-scale dengue outbreak in 2014. Coinciding with the 2014 outbreak, Tokyo's climate conditions permitted the amplification of Aedes vectors and the annual peak of vectorial capacity. Given suitable vectors and climate conditions in addition to increasing interconnectivity with endemic areas of Asia, Tokyo's 2014 outbreak did not come as a surprise and may foretell more to come.

  6. RNAi:antiviral therapy against dengue virus

    Institute of Scientific and Technical Information of China (English)

    Sobia Idrees; Usman A Ashfaq

    2013-01-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  7. Dengue shock syndrome in an infant.

    Science.gov (United States)

    Aurpibul, Linda; Khumlue, Punyawee; Issaranggoon na ayuthaya, Satja; Oberdorfer, Peninnah

    2014-01-01

    Dengue is a mosquito-borne infection affecting children and adults worldwide. In newborn infants, the dengue virus can cause diseases, especially in infants born to pregnant women hospitalised with dengue or postpartum women with fever. The authors report a case of a term newborn infant who presented with haemodynamic instability and thrombocytopaenia at the age of 7 days, without a history of clinical dengue infection in the mother. The physical examination revealed an afebrile and drowsy infant with a petechial rash all over the body and ecchymosis on both palms and soles. The authors confirmed the diagnosis using the dengue NS1 antigen on the first day of admission. The treatment included fluid management and platelet transfusion. The patient recovered well and was discharged from the hospital on the 10th day of hospitalisation. PMID:25073530

  8. The prevention and control of dengue after Typhoon Haiyan

    OpenAIRE

    Charito Aumentado; Boyd Roderick Cerro; Leonido Olobia; Lyndon Lee Suy; Aldrin Reyes; Pahalagedera HD Kusumawathie; Maria Sagrado; Julie Lyn Hall; Rabindra Abeyasinghe; Alice Ruth Foxwell; Vestergaard, Lasse S

    2015-01-01

    Objective: Many of the areas in the Philippines affected by Typhoon Haiyan are endemic for dengue; therefore, dengue prevention was a priority in the initial post-disaster risk assessment. We describe the dengue prevention and response strategies applied after Haiyan. Methods: The dengue response was implemented by a wide range of national and international stakeholders. Priorities included the rapid re-establishment of an effective surveillance system to quickly identify new dengue case...

  9. Dengue Expansion in Africa—Not Recognized or Not Happening?

    OpenAIRE

    Jaenisch, Thomas; Junghanss, Thomas; Wills, Bridget; Brady, Oliver J; Eckerle, Isabella; Farlow, Andrew; Simon I. Hay; Philip J McCall; Messina, Jane P; Ofula, Victor; Sall, Amadou A.; Sakuntabhai, Anavaj; Velayudhan, Raman; Wint, G.R. William; Zeller, Herve

    2014-01-01

    An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established ...

  10. Dengue Fever With Rectus Sheath Hematoma: A Case Report

    OpenAIRE

    Sharma, Anurag; Bhatia, Sonia; Singh, Rajendra Pratap; Malik, Gaurav

    2014-01-01

    Dengue fever, also known as breakbone fever, is an infectious tropical disease caused by the Dengue virus. It is associated with a number of complications, which are well documented. However, Dengue fever associated with rectus sheath hematoma (RSH) is a very rare complication. Only one case report has been published prior supporting the association of Dengue fever with RSH. We report a case of Dengue fever who presented with RSH and was successfully treated conservatively. RSH is also an unc...

  11. Unusual Presentation of Dengue Fever Leading to Unnecessary Appendectomy

    OpenAIRE

    Lovekesh Kumar; Mahendra Singh; Ashish Saxena; Yuvraj Kolhe; Karande, Snehal K.; Narendra Singh; Venkatesh, P.; Rambabu Meena

    2015-01-01

    Dengue fever is the most important arbovirus illness with an estimated incidence of 50–100 million cases per year. The common symptoms of dengue include fever, rash, malaise, nausea, vomiting, and musculoskeletal pain. Dengue fever may present as acute abdomen leading to diagnostic dilemma. The acute surgical complications of dengue fever include acute pancreatitis, acute acalculous cholecystitis, nonspecific peritonitis, and acute appendicitis. We report a case of dengue fever that mimicked ...

  12. Development of ASSURE® Dengue IgA Rapid Test for the Detection of Anti-dengue IgA from Dengue Infected Patients

    OpenAIRE

    Yun Ying Tan; Sekaran, Shamala D.; Seok Mui Wang; Firoz Ahmed; Anowar Hossain; Bijon Kumar Sil

    2011-01-01

    Background: Rapid and early dengue diagnosis is essential for patient management and early disease intervention. MP Diagnostics ASSURE® Dengue IgA Rapid Test (Dengue IgA RT) was developed for the rapid detection of anti-dengue IgA in patients′ biological samples. The performance of Dengue IgA RT was examined using multiple categories of well-characterized samples. Materials and Methods: Dengue IgA RT was designed and developed. Following characterization of samples by reference ELISAs, the pe...

  13. Optimization of Dengue Immunoassay by Label-Free Interferometric Optical Detection Method

    Directory of Open Access Journals (Sweden)

    María F. Laguna

    2014-04-01

    Full Text Available In this communication we report a direct immunoassay for detecting dengue virus by means of a label-free interferometric optical detection method. We also demonstrate how we can optimize this sensing response by adding a blocking step able to significantly enhance the optical sensing response. The blocking reagent used for this optimization is a dry milk diluted in phosphate buffered saline. The recognition curve of dengue virus over the proposed surface sensor demonstrates the capacity of this method to be applied in Point of Care technology.

  14. STUDY OF BRADYCARDIA IN DENGUE FEVER

    Directory of Open Access Journals (Sweden)

    Ramesh

    2014-03-01

    Full Text Available BACKGROUND AND OBJECTIVES: All the four serotypes of dengue virus are found in our country. Case fatality rates in endemic countries like India are 2.5%. During epidemics of dengue, attack rates among susceptible are 40-90%. Early recognition and prompt treatment are vital if disease related morbidity and mortality are to be limited. Clinical features that can be used in the initial assessment of febrile patients are essential tools for clinicians, especially in limited resource settings. Awareness of bradycardia as a clinical finding, could help in the early recognition of dengue and potentially reduce complications and death. METHOD AND RESULTS: The study was conducted in the Department of Medicine, Mysore Medical College & Research Institute, Mysore from the period of July 2010 to December 2010 who met the inclusion and exclusion criteria. A total of 100 patients of Dengue fever were analyzed. The most common age group affected in our study was 20-39 years (53%. The clinical spectrum of cases included 22% cases of Dengue fever (DF, 72% cases of Dengue Hemorrhagic fever (DHF, 6% cases of Dengue Shock Syndrome (DSS. Clinical pulse rate distribution amongst cases showed 27% with bradycardia, 61% with relative bradycardia, and 12% with tachycardia. Electrocardiographic changes in our study showed 37% with sinus bradycardia, 48% with normal sinus rhythm, 1% with first degree heart block, and 14% with sinus tachycardia. CONCLUSION: Bradycardia was a predominant occurrence amongst total of 100 cases of Dengue fever analyzed. 88% of the cases had bradycardia. (61% had relative bradycardia and 27% bradycardia. Majority of the patients on ECG showed sinus bradycardia (37% and normal sinus rhythm (48%. Hence, awareness of bradycardia as a clinical finding, can help in the early recognition of dengue and potentially reduce complications and death associated with dengue virus infection.

  15. Dengue encephalitis with predominant cerebellar involvement: Report of eight cases with MR and CT imaging features

    International Nuclear Information System (INIS)

    CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. (orig.)

  16. Dengue encephalitis with predominant cerebellar involvement: Report of eight cases with MR and CT imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Hegde, Vinay; Bhat, Maya; Prasad, Chandrajit; Gupta, A.K.; Saini, Jitender [National Institute of Mental Health and Neurosciences, Department of Neuroimaging and Interventional Radiology, Bangalore, Karnataka (India); Aziz, Zarina [Sri Sathya Sai Institute of Medical Science, Department of Radiology, Bangalore (India); Kumar, Sharath [Apollo Hospital, Department of Neuroradiology, Bangalore (India); Netravathi, M. [National Institute of Mental Health and Neurosciences, Department of Neurology, Bangalore (India)

    2014-11-01

    CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8-42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases. A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. (orig.)

  17. The use of rapid dengue diagnostic tests in a routine clinical setting in a dengue-endemic area of Colombia

    OpenAIRE

    Lyda Osorio; Marcela Uribe; Gloria Ines Ardila; Yaneth Orejuela; Margarita Velasco; Anilza Bonelo; Beatriz Parra

    2015-01-01

    There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were ...

  18. Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India

    OpenAIRE

    Guleria Randeep; Dar Lalit; Diddi Kavita; Pandey Anubhav; Chahar Harendra S; Bharaj Preeti; Kabra Sushil K; Broor Shobha

    2008-01-01

    Abstract Background Co-circulation of multiple dengue virus serotypes has been reported from many parts of the world including India, however concurrent infection with more than one serotype of dengue viruses in the same individual is rarely documented. An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) occurred in and around Delhi in 2006. This is the first report from India with high percentage of concurrent infections with different dengue virus serotypes circulating d...

  19. γδ T cell-mediated antibody-dependent cellular cytotoxicity with CD19 antibodies assessed by an impedance-based label-free real-time cytotoxicity assay

    Directory of Open Access Journals (Sweden)

    Ursula Jördis Eva Seidel

    2014-12-01

    Full Text Available γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation (SCT strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC with monoclonal antibodies (mAbs. These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL. To evaluate combination of human γδ T cells with CD19 antibodies for immunotherapy of B-lineage ALL, γδ T cells were expanded after a GMP-compliant protocol and ADCC of both primary and expanded γδ T cells with an Fc optimized CD19 antibody (4G7SDIE and a bispecific antibody with the specificities CD19 and CD16 (N19-C16 was evaluated in CD107a degranulation assays and intracellular cytokine staining (ICS. CD107a, TNF-α and IFN-γ expression of primary γδ T cells were significantly increased and correlated with CD16-expression of γδ T cells. γδ T cells highly expressed CD107a after expansion and no further increased expression by 4G7SDIE and N19-C16 was measured. Cytotoxicity of purified expanded γδ T cells targeting CD19-expressing cells was assessed in both europium-TDA release and in an impedance-based label-free method (using the xCELLigence system measuring γδ T cell lysis in real-time. Albeit in the 2 h end-point europium-TDA release assay no increased lysis was observed, in real-time xCELLigence assays both significant antibody-independent cytotoxicity and ADCC of γδ T cells were observed. The xCELLigence system outperformed the end-point europium-TDA release assay in sensitivity and allows drawing of conclusions to lysis kinetics of γδ T cells over prolonged periods of time periods. Combination of CD19 antibodies with primary as well as expanded γδ T cells exhibits an promising approach, which may enhance clinical outcome of patients with pediatric B-lineage ALL and

  20. γδ T Cell-Mediated Antibody-Dependent Cellular Cytotoxicity with CD19 Antibodies Assessed by an Impedance-Based Label-Free Real-Time Cytotoxicity Assay.

    Science.gov (United States)

    Seidel, Ursula Jördis Eva; Vogt, Fabian; Grosse-Hovest, Ludger; Jung, Gundram; Handgretinger, Rupert; Lang, Peter

    2014-01-01

    γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) with monoclonal antibodies (mAbs). These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL). To evaluate combination of human γδ T cells with CD19 antibodies for immunotherapy of B-lineage ALL, γδ T cells were expanded after a GMP-compliant protocol and ADCC of both primary and expanded γδ T cells with an Fc-optimized CD19 antibody (4G7SDIE) and a bi-specific antibody with the specificities CD19 and CD16 (N19-C16) was evaluated in CD107a-degranulation assays and intracellular cytokine staining. CD107a, TNFα, and IFNγ expression of primary γδ T cells were significantly increased and correlated with CD16-expression of γδ T cells. γδ T cells highly expressed CD107a after expansion and no further increased expression by 4G7SDIE and N19-C16 was measured. Cytotoxicity of purified expanded γδ T cells targeting CD19-expressing cells was assessed in both europium-TDA release and in an impedance-based label-free method (using the xCELLigence system) measuring γδ T cell lysis in real-time. Albeit in the 2 h end-point europium-TDA release assay no increased lysis was observed, in real-time xCELLigence assays both significant antibody-independent cytotoxicity and ADCC of γδ T cells were observed. The xCELLigence system outperformed the end-point europium-TDA release assay in sensitivity and allows drawing of conclusions to lysis kinetics of γδ T cells over prolonged periods of time periods. Combination of CD19 antibodies with primary as well as expanded γδ T cells exhibits a promising approach, which may enhance clinical outcome of patients with pediatric B-lineage ALL and requires clinical

  1. An epidemiological study of dengue in Delhi, India.

    Science.gov (United States)

    Vikram, Kumar; Nagpal, B N; Pande, Veena; Srivastava, Aruna; Saxena, Rekha; Anvikar, Anup; Das, Aparup; Singh, Himmat; Anushrita; Gupta, Sanjeev K; Tuli, N R; Telle, Olivier; Yadav, N K; Valecha, Neena; Paul, Richard

    2016-01-01

    Delhi, the capital of India, is an important metropolitan hub for major financial and sociocultural exchanges, offering challenging threats to current public health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed a significant menace to the existing dengue control policies. To reform the control strategies and take timely intervention to prevent future epidemics, an epidemiological study on the proportion of both asymptomatic and symptomatic dengue infections in selected population was conducted. The aim of the study was to investigate and assess the epidemiology of dengue infection and to estimate the proportion of asymptomatic and symptomatic dengue infections in Delhi. In this study, around 50 confirmed dengue cases, a total of 2125 individuals as household and neighbourhood contacts, with or without dengue febrile illness, were finger pricked and serologically detected as dengue positive or negative using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG combo test, which detected dengue virus antigen and antibodies to dengue virus in human blood. Out of 2125 individuals, 768 (36.1%) individuals showed positive dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue infections. Higher percentage of IgG was found in age groups 15-24 years and 25-50 years (36% each). Infants (dengue infection was either primary or secondary. On the basis of these results, it may be hypothesized that there are large number of asymptomatic dengue infections in the community as compared to reported symptomatic cases in Delhi. For the effective control of dengue transmission in such community like Delhi where dengue epidemics have frequently been encountered, it is essential to ascertain the proportion of asymptomatic dengue infections which may act as a reservoir for dengue transmission, as well as threat for developing dengue haemorrhagic fever (DHF). PMID:26433076

  2. An epidemiological study of dengue in Delhi, India.

    Science.gov (United States)

    Vikram, Kumar; Nagpal, B N; Pande, Veena; Srivastava, Aruna; Saxena, Rekha; Anvikar, Anup; Das, Aparup; Singh, Himmat; Anushrita; Gupta, Sanjeev K; Tuli, N R; Telle, Olivier; Yadav, N K; Valecha, Neena; Paul, Richard

    2016-01-01

    Delhi, the capital of India, is an important metropolitan hub for major financial and sociocultural exchanges, offering challenging threats to current public health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed a significant menace to the existing dengue control policies. To reform the control strategies and take timely intervention to prevent future epidemics, an epidemiological study on the proportion of both asymptomatic and symptomatic dengue infections in selected population was conducted. The aim of the study was to investigate and assess the epidemiology of dengue infection and to estimate the proportion of asymptomatic and symptomatic dengue infections in Delhi. In this study, around 50 confirmed dengue cases, a total of 2125 individuals as household and neighbourhood contacts, with or without dengue febrile illness, were finger pricked and serologically detected as dengue positive or negative using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG combo test, which detected dengue virus antigen and antibodies to dengue virus in human blood. Out of 2125 individuals, 768 (36.1%) individuals showed positive dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue infections. Higher percentage of IgG was found in age groups 15-24 years and 25-50 years (36% each). Infants (dengue infection was either primary or secondary. On the basis of these results, it may be hypothesized that there are large number of asymptomatic dengue infections in the community as compared to reported symptomatic cases in Delhi. For the effective control of dengue transmission in such community like Delhi where dengue epidemics have frequently been encountered, it is essential to ascertain the proportion of asymptomatic dengue infections which may act as a reservoir for dengue transmission, as well as threat for developing dengue haemorrhagic fever (DHF).

  3. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Gábor Szalóki

    Full Text Available P-glycoprotein (Pgp extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR. The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA. The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX in KB-V1 (Pgp+ cells in vitro almost to the level of KB-3-1 (Pgp- cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs, it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC.

  4. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

    Science.gov (United States)

    Szalóki, Gábor; Krasznai, Zoárd T; Tóth, Ágnes; Vízkeleti, Laura; Szöllősi, Attila G; Trencsényi, György; Lajtos, Imre; Juhász, István; Krasznai, Zoltán; Márián, Teréz; Balázs, Margit; Szabó, Gábor; Goda, Katalin

    2014-01-01

    P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA)). The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX) in KB-V1 (Pgp+) cells in vitro almost to the level of KB-3-1 (Pgp-) cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID) mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET) based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs), it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC). PMID:25238617

  5. Environmental and Socio-Demographic Determinants of Dengue Fever in Colombo City, Sri Lanka

    Science.gov (United States)

    Tipre, Meghan; Luvall, Jeffrey; Haque, Akhlaque; McClure, Leslie; Zaitchik, Ben; Sathiakumar, Nalini

    2014-01-01

    Dengue fever has increased exponentially in Sri Lanka, from 24.4 cases per 100,000 in 2003 to 165.3 per 100,000 population in 2013. Although early warning systems using predictor models have been previously developed in other settings, it is important to develop such models in each local setting. Further, the ability of these models to be applicable at smaller geographic units will enhance current vector control and disease surveillance measures. The aim of this paper was to identify environmental and socio-economic status (SES) risk factors that may predict dengue fever at the Gram Niladhari Divisions (GND) level (smallest administrative unit) in Colombo city, Sri Lanka. These factors included landcover classes, amount of vegetation, population density, water access and neighborhood SES as determined by roof type. A geographically weighted regression (GWR) was used to develop the prediction model. A total 55 GND units covering an area of 37 sq km were investigated. We found that GND units with decreased vegetation, higher built-up area, higher population density and poor access to tap-water supply were associated with high risk of dengue; the pertinent GND units were concentrated in the center of the city. This is the first study in Sri Lanka to include both environmental and socio-demographic factors in prediction models for dengue fever. The methodology may be useful in enhancing ongoing dengue fever control measures in the country, and to be extended to other countries in the region that have an increasing incidence of dengue fever.

  6. Human antibody response to dengue virus: implications for dengue vaccine design.

    Science.gov (United States)

    Moi, Meng Ling; Takasaki, Tomohiko; Kurane, Ichiro

    2016-01-01

    Dengue, a global health threat, is a leading cause of morbidity and mortality in most tropical and subtropical countries. Dengue can range from asymptomatic, relatively mild dengue fever to severe and life-threatening dengue hemorrhagic fever. Disease severity and outcome is largely associated with the host immune response. Several candidate vaccines in clinical trials appear promising as effective measures for dengue disease control. Vaccine development has been hampered by safety and efficacy issues, driven by a lack of understanding of the host immune response. This review focuses on recent research findings on the dengue host immune response, particularly in humans, and the relevance of these findings to challenges in vaccine development. PMID:27398060

  7. DengueTools: innovative tools and strategies for the surveillance and control of dengue

    Directory of Open Access Journals (Sweden)

    Annelies Wilder-Smith

    2012-03-01

    Full Text Available Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of ‘Comprehensive control of Dengue fever under changing climatic conditions’. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named ‘DengueTools’ to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas: Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring. Research area 2: Develop novel strategies to prevent dengue in children. Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of ‘DengueTools’. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant

  8. Decreases in dengue transmission may act to increase the incidence of dengue hemorrhagic fever

    OpenAIRE

    Nagao, Yoshiro; Koelle, Katia

    2008-01-01

    Dengue hemorrhagic fever (DHF) is a potentially fatal manifestation of an infection with the mosquito-borne dengue virus. Because of the social and economic costs of DHF, many countries in Asia and South America have initiated public health measures aimed at vector control. Despite these measures, DHF incidence rates do not appear to be declining. The effectiveness of vector control in reducing dengue transmissibility has thereby been questioned. Here, we revisit this conclusion using epidemi...

  9. Economic burden of dengue infections in India.

    Science.gov (United States)

    Garg, Pankaj; Nagpal, Jitender; Khairnar, Prakash; Seneviratne, Suranjith L

    2008-06-01

    Dengue infections are a significant cause of morbidity and mortality and lead to adverse economic effects in many developing tropical countries. In this study, we estimated the economic burden faced by India during the 2006 dengue epidemic. Costs incurred in managing a cohort of serologically confirmed dengue patients at a tertiary-level private hospital in north India were calculated. The median cost of treatment per hospitalised dengue patient was US$432.2 (95% CI US$343.6-625). A sensitivity analysis was performed to estimate the costs to the health system in India using a regression model. Variables with potentially large variations, including the ratio of unreported to reported cases and of hospitalised to ambulatory cases, the proportion requiring transfusions, loss of economic activities due to loss of workdays and deaths, were used. The average total economic burden was estimated to be US$27.4 million (95% CI US$25.7-29.1 million). Costs in the private heath sector were estimated to be almost four times public sector expenditures. Considerable economic losses (at a macro level) are incurred by developing countries like India during each dengue epidemic. Accurate estimates of the proportions of reported to unreported and of hospitalised to ambulatory dengue cases in India are needed to refine further the estimates of financial burden due to dengue in India. PMID:18402995

  10. Dengue: a new challenge for neurology

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    2012-11-01

    Full Text Available Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world’s population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial.

  11. Vaccines and immunization strategies for dengue prevention.

    Science.gov (United States)

    Liu, Yang; Liu, Jianying; Cheng, Gong

    2016-01-01

    Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

  12. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  13. [Development of immunizing agents against dengue].

    Science.gov (United States)

    López Antuñano, F J; Mota, J

    2000-05-01

    The four serotypes of dengue flaviviruses are transmitted mainly by the Aedes aegypti mosquito, and some epidemics have been attributed to Ae. albopictus, Ae. polynesiensis, and various species of the Ae. scutellaris complex. The risk factors involved in dengue mortality and morbidity are related to the human host (genetic characteristics of infected persons; lifestyles, immune status, and health conditions of people; basic sanitation of dwellings; and water supply) and to the virus (genetic variability between and among serotypes, different pathogenicities, and geographic distribution). Notwithstanding the lack of knowledge of the immunopathobiology of dengue fever, important advances have been made in terms of a protective immune response, using attenuated dengue viruses or antigens produced by means of recombinant technologies. Efforts have been made since the 1940s to develop dengue vaccines. Immunity acquired from natural infection is specific for each serotype, and as many as three different serotype infections have been reported in one individual. For this reason, a tetravalent vaccine may likely be needed. Candidate vaccines against the four serotypes have been tested in volunteers and have proven to be immunogenic and safe. Although attenuated live virus vaccines are promising, more study is needed regarding their effectiveness and safety. Currently, several studies are ongoing to develop dengue vaccines using antigens from structural proteins (particularly E glycoprotein) and nonstructural proteins, with recombinant DNA technology and other biomolecular technologies. With the same goal, various expression vectors are being used, including Escherichia coli, baculovirus, vaccinia virus, and yellow fever virus. Unfortunately, no satisfactory results have been obtained in humans. The need for effective dengue vaccines is great, given the serious worldwide problem of the transmission of the four serotypes. Effective immunization against dengue would contribute

  14. Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence: re-introduction of dengue-3 associated to mild febrile illness and primary infection

    OpenAIRE

    Raquel Elvira Ocazionez; Fabián Mauricio Cortés; Luis Angel Villar; Sergio Yebrail Gómez

    2006-01-01

    We have investigated the temporal distribution of dengue (DEN) virus serotypes in the department (state) of Santander, Colombia, in relation to dengue incidence, infection pattern, and severity of disease. Viral isolation was attended on a total of 1452 acute serum samples collected each week from 1998 to 2004. The infection pattern was evaluated in 596 laboratory-positive dengue cases using an IgG ELISA, and PRNT test. The dengue incidence was documented by the local health authority. Predom...

  15. Comparative Amino Acid Sequences of Dengue Viruses

    OpenAIRE

    Haishi, Shozo; TANAKA Mariko; Igarashi, Akira

    1990-01-01

    Amino acid (AA) sequences of 4 serotype of dengue viruses deduced from their nucleotide (nt) sequences of genomic RNA were analyzed for each genome segment and each stretch of 10 AA residues. Precursor of membrane protein (pM), and 4 nonstructural proteins (NS1, NS3, NS4B, NS5) were highly conserved, while another nonstructural protein (NS2A) was least conserved among 5 strains of dengue viruses. When homology was compared among heterotypic viruses, type 1 and type 3 dengue viruses showed clo...

  16. Dengue infection presenting as acute hypokalemic quadriparesis

    Directory of Open Access Journals (Sweden)

    N Gupta

    2014-01-01

    Full Text Available Dengue infection is one of the most common viral hemorrhagic fevers seen in the tropical countries, including India. Its presentation varies from an acute self-resolving febrile illness to life-threatening hemorrhagic shock and multiorgan dysfunction leading to death. Neurological presentations are uncommon and limited to case reports only. Most common neurological manifestations being encephalitis, acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting feature of dengue is extremely rare. Here, we report this case of a 33-year-old female, who presented with hypokalemic quadriparesis and was subsequently diagnosed as dengue infection.

  17. [Imported dengue: an emerging arbovirosis in Spain].

    Science.gov (United States)

    Ramos Geldres, T T; García López-Hortelano, M; Baquero-Artigao, F; Montero Vega, D; López Quintana, B; Mellado Peña, M J

    2015-01-01

    Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis. PMID:24880817

  18. Dengue Haemorrhagic Fever presenting as Acute Abdomen

    OpenAIRE

    Al-Araimi, Hanaa; Al-Jabri, Amal; Mehmoud, Arshad; Al-Abri, Seif

    2011-01-01

    We describe a case of a 38 year-old Sri Lankan female who was referred to the surgeon on call with a picture of acute abdomen. She presented with a three-day history of fever, headache, abdominal pain and diarrhoea; however, the physical examination was not consistent with acute abdomen. Her platelet count was 22 ×109/L. A diagnosis of dengue haemorrhagic fever (DHF) was made and dengue serology was positive. Dengue epidemics have been associated with a variety of gastrointestinal symptoms an...

  19. Two Decades of Dengue in Malaysia

    OpenAIRE

    Lam, S. K.

    1994-01-01

    Dengue is endemic in Malaysia and the first case was documented in 1902. The disease was made notifiable in 1973 and the first outbreak of dengue haemorrhagic fever was reported in 1962. During the decade of 1973-1982, there were 12,077 dengue cases with a case fatality rate of 3.38%. In the following decade of 1983-1992, the number of reported cases increased to 26,361 but the case fatality rate dropped to 0.55%. The increase in incidence could be due to rising economy, rapid industrializati...

  20. The use of rapid dengue diagnostic tests in a routine clinical setting in a dengue-endemic area of Colombia.

    Science.gov (United States)

    Osorio, Lyda; Uribe, Marcela; Ardila, Gloria Ines; Orejuela, Yaneth; Velasco, Margarita; Bonelo, Anilza; Parra, Beatriz

    2015-06-01

    There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.

  1. Unusual Presentation of Dengue Fever Leading to Unnecessary Appendectomy.

    Science.gov (United States)

    Kumar, Lovekesh; Singh, Mahendra; Saxena, Ashish; Kolhe, Yuvraj; Karande, Snehal K; Singh, Narendra; Venkatesh, P; Meena, Rambabu

    2015-01-01

    Dengue fever is the most important arbovirus illness with an estimated incidence of 50-100 million cases per year. The common symptoms of dengue include fever, rash, malaise, nausea, vomiting, and musculoskeletal pain. Dengue fever may present as acute abdomen leading to diagnostic dilemma. The acute surgical complications of dengue fever include acute pancreatitis, acute acalculous cholecystitis, nonspecific peritonitis, and acute appendicitis. We report a case of dengue fever that mimicked acute appendicitis leading to unnecessary appendectomy. A careful history examination for dengue-related signs, and serial hemogram over the first 3-4 days of disease may prevent unnecessary appendectomy. PMID:26167314

  2. Unusual Presentation of Dengue Fever Leading to Unnecessary Appendectomy

    Directory of Open Access Journals (Sweden)

    Lovekesh Kumar

    2015-01-01

    Full Text Available Dengue fever is the most important arbovirus illness with an estimated incidence of 50–100 million cases per year. The common symptoms of dengue include fever, rash, malaise, nausea, vomiting, and musculoskeletal pain. Dengue fever may present as acute abdomen leading to diagnostic dilemma. The acute surgical complications of dengue fever include acute pancreatitis, acute acalculous cholecystitis, nonspecific peritonitis, and acute appendicitis. We report a case of dengue fever that mimicked acute appendicitis leading to unnecessary appendectomy. A careful history examination for dengue-related signs, and serial hemogram over the first 3-4 days of disease may prevent unnecessary appendectomy.

  3. Oviposition site selection by the dengue vector Aedes aegypti and its implications for dengue control.

    Directory of Open Access Journals (Sweden)

    Jacklyn Wong

    Full Text Available BACKGROUND: Because no dengue vaccine or antiviral therapy is commercially available, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Traditional models of Ae. aegypti assume that population dynamics are regulated by density-dependent larval competition for food and little affected by oviposition behavior. Due to direct impacts on offspring survival and development, however, mosquito choice in oviposition site can have important consequences for population regulation that should be taken into account when designing vector control programs. METHODOLOGY/PRINCIPAL FINDINGS: We examined oviposition patterns by Ae. aegypti among 591 naturally occurring containers and a set of experimental containers in Iquitos, Peru. Using larval starvation bioassays as an indirect measure of container food content, we assessed whether females select containers with the most food for their offspring. Our data indicate that choice of egg-laying site is influenced by conspecific larvae and pupae, container fill method, container size, lid, and sun exposure. Although larval food positively influenced oviposition, our results did not support the hypothesis that females act primarily to maximize food for larvae. Females were most strongly attracted to sites containing immature conspecifics, even when potential competitors for their progeny were present in abundance. CONCLUSION/SIGNIFICANCE: Due to strong conspecific attraction, egg-laying behavior may contribute more to regulating Ae. aegypti populations than previously thought. If highly infested containers are targeted for removal or larvicide application, females that would have preferentially oviposited in those sites may instead distribute their eggs among other suitable, previously unoccupied containers. Strategies that kill mosquitoes late in their development (i.e., insect growth regulators that kill pupae rather than larvae will enhance vector

  4. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  5. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the...

  6. Dengue: an update on treatment options.

    Science.gov (United States)

    Chan, Candice Y Y; Ooi, Eng Eong

    2015-01-01

    Dengue is the most important mosquito-borne viral pathogen globally, with approximately 100 million cases of acute dengue annually. Infection can result in severe, life-threatening disease. Currently, there is no effective vaccine or licensed antiviral. Management is primarily supportive with fluids. Direct antiviral therapies that reduce dengue severity could be useful although these would need to inhibit all four viral serotypes effectively. This review focuses on the interventions that currently considered the gold standard in case management as well as exploratory therapies that have been studied in clinical trials. Although antiviral drug and therapeutic antibodies for dengue remain a work in progress, these studies have produced some promising results and may have the potential to be future drugs. PMID:26594048

  7. Dengue e dengue hemorrágico: aspectos do manejo na unidade de terapia intensiva Dengue and dengue hemorrhagic fever: management issues in an intensive care unit

    Directory of Open Access Journals (Sweden)

    Sunit Singhi

    2007-05-01

    Full Text Available OBJETIVOS: Descrever a epidemiologia, as características clínicas e o tratamento do dengue e das síndromes do choque associadas ao dengue. FONTES DOS DADOS: Para esta revisão de literatura, foi feita uma pesquisa no Pubmed e nos websites da Organização Mundial da Saúde (OMS e OPAS usando os termos dengue e síndrome do choque associada ao dengue. A informação foi complementada com a experiência pessoal dos autores. SÍNTESE DOS DADOS: O dengue é a mais importante doença viral transmitida por artrópodos em seres humanos. A doença se manifesta de diversas formas, variando desde uma síndrome viral não-diferenciada até febre hemorrágica e choque grave. O dengue é uma enfermidade autolimitada, não específica, caracterizada por febre, cefaléia, mialgia, e sintomas constitucionais. As formas mais graves (febre hemorrágica e síndrome do choque podem levar a um comprometimento multissistêmico e ao óbito. O diagnóstico precoce e um acompanhamento contínuo do agravamento e da resposta ao tratamento são necessários em todos os casos. A OMS recomenda uma abordagem escalonada para o manejo, adequada para as formas mais leves e para o choque precoce. Nas formas mais graves, é preciso uma abordagem agressiva de reanimação com fluidos e de suporte à falência de órgãos em pacientes em estado crítico. As pesquisas sobre as diferenças fisiopatológicas entre o choque do dengue e o choque séptico, seleção de fluidos, agentes inotrópicos e técnicas de suporte a órgãos podem beneficiar os pacientes em estado crítico. CONCLUSÕES: Não há uma terapia específica para infecções causadas pelo dengue. Um bom tratamento de suporte pode salvar vidas mas, em última análise, as iniciativas de controle do vetor e de prevenção contra picadas do mosquito podem trazer os maiores benefícios.OBJECTIVES: To describe the epidemiology, clinical features and treatment of dengue fever and dengue shock syndrome. SOURCES: To prepare

  8. Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmission.

    Directory of Open Access Journals (Sweden)

    Louis Lambrechts

    Full Text Available The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses, including the most prevalent arboviral pathogen of humans, dengue virus (DENV. Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from "natural experiments" indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic

  9. Dengue Preceding Diabetic Ketoacidosis Dear Editor;

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2013-12-01

    Full Text Available Diabetic ketoacidosis (DKA is an important hyperglycemic complication of diabetes mellitus. Infection is confirmed as an important underlying etiology of DKA. Here, the author presents an interesting case of dengue preceding DKA. The case is a 61-year-old female presenting to the physician with the complaint of high fever without relief by self-prescription of acetaminophen. She had an underlying disease, diabetes mellitus (DM. Her body temperature was 39.4 degrees Celsius and her complete blood count showed an important finding: thrombocytopenia (platelet count = 85.000. The serological test was done and the diagnosis of dengue hemorrhagic fever was finally confirmed. This case was treated by standard fluid replacement therapy (normal saline regimen. On day 3, the patient developed new symptoms, frequent urination (more than 3 times in an hour, abdominal pain, nausea, vomiting and rapid breathing. Complete blood count was done but platelet count was within normal limit at this time. However, the urinalysis showed many positive findings, sugar 4+ and ketone 3+. Her additional blood chemistry results showed a blood glucose level of 454 mg/dL and positive serum ketone. The patient was finally diagnosed to have DKA and endocrinologists were consulted for the management. Of interest, this is a simple case of DKA but the interesting issue is the underlying condition leading to DKA in this patient. Although there are many reports confirming that infection can induce DKA, this is the first reported case of dengue preceding DKA. Indeed, there is a previous report from Thailand on a female patient presented to the physician with concurrent DKA and dengue infection (1. However, DM had not previously been diagnosed in the present case. The dengue infection is common in the tropical world and DM is also the important emerging health problem in this area. Some reports note that DM can be an aggravating factor in the development of dengue shock (2,3. There is

  10. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Veloso Henrique Horta

    2003-01-01

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  11. Dengue: a new challenge for neurology

    OpenAIRE

    Marzia Puccioni-Sohler; Marco Orsini; Cristiane N. Soares

    2012-01-01

    Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world’s population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturb...

  12. Dengue: muscle biopsy findings in 15 patients

    OpenAIRE

    S.M.F. Malheiros; Oliveira, A.S.B.; Schmidt, B.; J. G. Camargo Lima; A. A. Gabbai

    1993-01-01

    Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and ne...

  13. Negative selection algorithm for dengue outbreak detection

    OpenAIRE

    Mousavi, Maryam; BAKAR, Azuraliza ABU; ZAINUDIN, Suhaila; LONG, Zalizah AWANG; Sahani, Mazrura; VAKILIAN, Mohammadmahdi

    2012-01-01

    Dengue is a critical communicable and vector-borne disease and is becoming a serious concern in Malaysia. It is important to have an early detection system that could provide immediate action, such as the control of dengue transmission at a specific location. However, the available strategy and action may give long-term effects to the community since inaccurate decision making or prediction may lead to other circumstances. Moreover, the need to have a system that can detect the outbreak...

  14. Climate and Dengue Transmission: Evidence and Implications

    OpenAIRE

    Morin, Cory W.; Comrie, Andrew C.; Ernst, Kacey

    2013-01-01

    Background: Climate influences dengue ecology by affecting vector dynamics, agent development, and mosquito/human interactions. Although these relationships are known, the impact climate change will have on transmission is unclear. Climate-driven statistical and process-based models are being used to refine our knowledge of these relationships and predict the effects of projected climate change on dengue fever occurrence, but results have been inconsistent. Objective: We sought to identify ma...

  15. [Neonatal Dengue. Presentation of clinical cases].

    Science.gov (United States)

    Romero-Santacruz, Edith; Lira-Canul, Janeth Jaqueline; Pacheco-Tugores, Fredy; Palma-Chan, Adolfo Gonzalo

    2015-05-01

    Dengue is an infectious disease caused by a flavivirus, with four serotypes, transmitted by the mosquito Aedes aegypti. In Mexico it is a public health problem, especially in the region of central and southeast of the country. The disease can be asymptomatic or present serious forms and even death. It is confirmed by detection of the NS1 Antigen; IgM antibodies, polymerase chain reaction and virus isolation. The vertical transmission to de newborn has been little studied. 7 cases in neonates from November to December 2011 are reported. All patients were male, obtained by caesarean section between 34 and 40 weeks of gestation, whose mothers were enrolled with fever and symptoms associated with dengue disease and serology positive for dengue. Six with positive AgNS1 and one positive IgM; one mother died. All the newborns had positive serology for dengue, 4 with positive AgNS1 and 3 positive IgM. The clinical features of the newborn ranged from asymptomatic to one serious dengue fever, shock and hemorrhage. The symptomatic 6 attended with thrombocytopenia, changes in temperature and unspecific disturbance. The severity of mothers conditioned disrepair product at birth, but not with subsequent gravity of the new born. Vertical trasmission of dengue should be suspected in risk areas, to maintain vigilance and to give early treatment. Also is neccesary promote the realization of specific diagnostic and therapeutic guidelines to the neonatal period.

  16. Uncovering dengue in India: morbidity estimates

    Directory of Open Access Journals (Sweden)

    Ananda Amarasinghe

    2014-05-01

    Full Text Available Over the last few decades, reporting of dengue cases has dramatically spread over almost entire India but the disease burden is grossly under-estimated under the current surveillance system. This review based on literature searches in PubMed and Medline for the period 1961-2012 describes changing epidemiological patterns, emerging challenges to public health intervention for control of dengue transmission in India and estimates magnitude of under-reporting. The annual reported numbers in 10 selected states/Union Territories with the highest number of cases during the years 2008-2012 and the surveillance system estimated expansion factor of 8.9-9.6 derived from Thailand and Cambodia data respectively were used for new estimates of dengue morbidity in India. The reporting incidence of dengue is as low as 4/100,000 in 2012. The estimated crude incidence of dengue for 2012 is 53/100,000 to 58.83/100,000 and the country annual health care facility based case load would be around 700,000. India needs to expand surveillance activities to non-hospitalized cases and to the distribution and abundance of Aedes aegypti throughout country and review state and local vector control activities for Aedes aegypti and Aedes albopictus. Knowledge of vector prevalence is essential to estimate the geographical distribution of dengue infection and associated disease.

  17. The effects of urban growth on dengue

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Pereira Horta

    2014-09-01

    Full Text Available Objective: To analyze the spatial and temporal dynamics of dengue in Coronel Fabriciano, Minas Gerais State, Brazil, and to associate cases to the growth of urban areas and loss of natural areas in recent years. Methods: This is a descriptive, exploratory study, with a quantitative approach. Dengue cases of 2009 were obtained from the Health Municipal Secretariat, including the suspected and confirmed cases. Shape files were obtained, containing information about the municipal boundary, boundary of the urban area, census tracts, areas with buildings and natural areas. Based on the distribution of dengue cases, the Kernel estimator was used to measure data dispersion. Results: Dengue cases reported were georeferenced in GIS (Geographic Information System environment. The landscape showed changes in the units of urban area and pasture, as an urban growth over the pasture matrix. No changes were observed in the areas of remaining forest and eucalyptus. There are cases spatially spread with a tendency to form clusters. Conclusion: Cases of dengue were observed spatially clustered in the northern region of the city, where new neighborhoods have emerged in recent years, following the population growth without proper structure of urbanization and urban planning. In addition, urban growth have reduced the margin of watercourses providing a bare soil, suitable for accumulation of trash and formation of breeding sites for mosquitoes. Efficient public policies and appropriate urban planning might reduce the impact of dengue in endemic regions. doi: http://dx.doi.org/10.5020/18061230.2013.p539

  18. [Neonatal Dengue. Presentation of clinical cases].

    Science.gov (United States)

    Romero-Santacruz, Edith; Lira-Canul, Janeth Jaqueline; Pacheco-Tugores, Fredy; Palma-Chan, Adolfo Gonzalo

    2015-05-01

    Dengue is an infectious disease caused by a flavivirus, with four serotypes, transmitted by the mosquito Aedes aegypti. In Mexico it is a public health problem, especially in the region of central and southeast of the country. The disease can be asymptomatic or present serious forms and even death. It is confirmed by detection of the NS1 Antigen; IgM antibodies, polymerase chain reaction and virus isolation. The vertical transmission to de newborn has been little studied. 7 cases in neonates from November to December 2011 are reported. All patients were male, obtained by caesarean section between 34 and 40 weeks of gestation, whose mothers were enrolled with fever and symptoms associated with dengue disease and serology positive for dengue. Six with positive AgNS1 and one positive IgM; one mother died. All the newborns had positive serology for dengue, 4 with positive AgNS1 and 3 positive IgM. The clinical features of the newborn ranged from asymptomatic to one serious dengue fever, shock and hemorrhage. The symptomatic 6 attended with thrombocytopenia, changes in temperature and unspecific disturbance. The severity of mothers conditioned disrepair product at birth, but not with subsequent gravity of the new born. Vertical trasmission of dengue should be suspected in risk areas, to maintain vigilance and to give early treatment. Also is neccesary promote the realization of specific diagnostic and therapeutic guidelines to the neonatal period. PMID:26233977

  19. Seropositivity of Dengue Antibodies during Pregnancy

    Directory of Open Access Journals (Sweden)

    Nor Azlin Mohamed Ismail

    2014-01-01

    Full Text Available Purpose. Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM during pregnancy and its neonatal transmission in dengue seropositive women. Methods. Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM using an enzyme-linked immunosorbent assay (ELISA. Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive Care Unit (NICU were analyzed. Results. Out of 358 women recruited, about 128 (35.8% patients were seropositive. Twelve patients (3.4% had recent infections (IgM positive and another 116 women (32.4% were with past infections (IgG positive. All babies born to seropositive mothers had positive IgG paired cord blood; however, no IgM seropositivity was observed. All neonates had good Apgar scores and did not require NICU admission. Conclusion. In this study, 35.8% pregnant women were found to be dengue seropositive. However, transplacental transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.

  20. Comparison of real-time SYBR green dengue assay with real-time taqman RT-PCR dengue assay and the conventional nested PCR for diagnosis of primary and secondary dengue infection

    OpenAIRE

    Damodar Paudel; Richard Jarman; Kriengsak Limkittikul; Chonticha Klungthong; Supat Chamnanchanunt; Ananda Nisalak; Robert Gibbons; Watcharee Chokejindachai

    2011-01-01

    Background : Dengue fever and dengue hemorrhagic fever are caused by dengue virus. Dengue infection remains a burning problem of many countries. To diagnose acute dengue in the early phase we improve the low cost, rapid SYBR green real time assay and compared the sensitivity and specificity with real time Taqman® assay and conventional nested PCR assay. Aims: To develop low cost, rapid and reliable real time SYBR green diagnostic dengue assay and compare with Taqman real-time assay and conven...

  1. Rare case of acute dengue encephalitis with correlated MRI findings

    International Nuclear Information System (INIS)

    Dengue encephalitis is extremely rare, with most patients showing no significant abnormality on neuroimaging (CT/MRI). We report one of the very few documented cases of dengue encephalitis, with abnormal signal intensities on all major sequences on brain MRI.

  2. Platelet function alterations in dengue are associated with plasma leakage

    NARCIS (Netherlands)

    Michels, M.; Alisjahbana, B.; Groot, P.G. de; Indrati, A.R.; Fijnheer, R.; Puspita, M.; Dewi, I.M.; Wijer, L. van de; Boer, E.M. de; Roest, M.; Ven, A.J. van der; Mast, Q. de

    2014-01-01

    Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengu

  3. Dengue virus serotype 2 from a sylvatic lineage isolated from a patient with dengue hemorrhagic fever.

    Directory of Open Access Journals (Sweden)

    Jane Cardosa

    Full Text Available Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF with thrombocytopenia (12,000/ul and a raised hematocrit (29.5% above baseline in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.

  4. Transmission spectroscopy of dengue viral infection Transmission spectroscopy of dengue viral infection

    Science.gov (United States)

    Firdous, S.; Ahmed, M.; Rehman, A.; Nawaz, M.; Anwar, S.; Murtaza, S.

    2012-04-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 - 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 - 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 - 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients.

  5. Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial

    Science.gov (United States)

    Taurel, Anne-Frieda; Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki; Chotpitayasunondh, Tawee; Chong, Chee Kheong; Wartel, T. Anh; Beucher, Sophie; Frago, Carina; Moureau, Annick; Simmerman, Mark; Laot, Thelma; L’Azou, Maïna; Bouckenooghe, Alain

    2016-01-01

    Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions. PMID:27532617

  6. Implications of discordance in world health organization 1997 and 2009 dengue classifications in adult dengue.

    Directory of Open Access Journals (Sweden)

    Victor C Gan

    Full Text Available BACKGROUND: Revised dengue guidelines were published by the World Health Organization (WHO in 2009 addressing severe dengue cases not classified by dengue hemorrhagic fever (DHF and shock syndrome (DSS. METHODS AND PRINCIPAL FINDINGS: We conducted a retrospective cohort study to compare WHO 2009 and 1997 classifications using 1278 adult dengue cases confirmed by polymerase chain reaction assay from Singapore epidemics in 2004 and 2007 (predominantly serotype 1 and 2 respectively.DHF occurred in 14.3%, DSS 2.7% and severe dengue 16.0%. The two WHO dengue classifications were discordant in defining severe disease (p<0.001. Five DSS patients (15% were classified as non-severe dengue without warning signs. Of severe dengue patients, 107 did not fulfil DHF criteria. Of these, 14.9% had self-resolving isolated elevated aminotransferases, 18.7% gastrointestinal bleeding without hemodynamic compromise and 56.1% plasma leakage with isolated tachycardia. We compared both guidelines against requirement for intensive care including the single death in this series: all six had severe dengue; only four had DHF as two lacked bleeding manifestations but had plasma leakage. Increasing length of hospitalization was noted among severe cases with both classifications but the trend was only statistically significant for WHO 2009. Length of hospitalization was significantly longer for severe plasma leakage compared with severe bleeding or organ impairment. Requirement for hospitalization increased using WHO 2009 from 17.0% to 51.3%. CONCLUSIONS: While the WHO 2009 dengue classification is clinically useful, we propose retaining criteria for plasma leakage and hemodynamic compromise from WHO 1997, and refining definitions of severe bleeding and organ impairment to improve clinical relevance having found that differences in these accounted for the discordance between classifications. Findings from our retrospective study may be limited by the study site - a tertiary

  7. Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial.

    Science.gov (United States)

    Nealon, Joshua; Taurel, Anne-Frieda; Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki; Chotpitayasunondh, Tawee; Chong, Chee Kheong; Wartel, T Anh; Beucher, Sophie; Frago, Carina; Moureau, Annick; Simmerman, Mark; Laot, Thelma; L'Azou, Maïna; Bouckenooghe, Alain

    2016-08-01

    Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.

  8. Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial.

    Science.gov (United States)

    Nealon, Joshua; Taurel, Anne-Frieda; Capeding, Maria Rosario; Tran, Ngoc Huu; Hadinegoro, Sri Rezeki; Chotpitayasunondh, Tawee; Chong, Chee Kheong; Wartel, T Anh; Beucher, Sophie; Frago, Carina; Moureau, Annick; Simmerman, Mark; Laot, Thelma; L'Azou, Maïna; Bouckenooghe, Alain

    2016-08-01

    Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2-14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14's active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions. PMID:27532617

  9. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control ...

  10. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

    OpenAIRE

    Om Parkash; Rafidah Hanim Shueb

    2015-01-01

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory ...

  11. Dengue disease diagnosis: A puzzle to be solved

    OpenAIRE

    Jaime Eduardo Castellanos; Carolina Coronel-Ruiz

    2014-01-01

    Dengue is an infection caused by dengue virus and is the most important arthropod transmitted viral disease in the world, causing near 100 million cases and 50 000 fatalities each year. Health authorities believe that these numbers will grow in coming years. In Colombia, almost 600 municipalities are in regions with Aedes aegypti circulation, and the presence of four dengue serotypes has been demonstrated. Despite the increasing knowledge about disease pathogenesis and the dengue virus, some ...

  12. Dengue-specific subviral nanoparticles: design, creation and characterization

    OpenAIRE

    Khetarpal, Niyati; Poddar, Ankur; Nemani, Satish K; Dhar, Nisha; Patil, Aravind; Negi, Priyanka; Perween, Ashiya; Viswanathan, Ramaswamy; Lünsdorf, Heinrich; Tyagi, Poornima; Raut, Rajendra; Arora, Upasana; Jain, Swatantra K.; Rinas, Ursula; Swaminathan, Sathyamangalam

    2013-01-01

    Background Dengue is today the most significant of arboviral diseases. Novel tools are necessary to effectively address the problem of dengue. Virus-like particles (VLP) offer a versatile nanoscale platform for developing tools with potential biomedical applications. From the perspective of a potentially useful dengue-specific tool, the dengue virus envelope protein domain III (EDIII), endowed with serotype-specificity, host receptor recognition and the capacity to elicit virus-neutralizing a...

  13. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case cont...

  14. Early molecular markers predictive of dengue hemorrhagic fever

    OpenAIRE

    Carlos E Calzavara-Silva; Ana L.V. Gomes; Rita C.C. Maia; Bartolomeu Acioli-Santos; Gil, Laura H.V.G.; Ernesto T.A. Marques Jr.

    2009-01-01

    The management of acute dengue patients during outbreaks is a challenging problem. Most of the dengue fever cases are benign, but some cases develop into a severe and possibly lethal vasculopathy, known as dengue hemorrhagic fever. Early symptoms of dengue and hemorrhagic fever are very similar. An early differential diagnosis is needed to predict which of these two clinical presentations is crucial to proper patient care and public health management. This study evaluates the predictive poten...

  15. A rare but potentially lethal complication of dengue

    Institute of Scientific and Technical Information of China (English)

    Yingjuan Mok; Jessica Quah; Chuin Siau

    2013-01-01

    Severe rhabdomyolysis is an uncommon but potentially fatal complication of dengue fever that is not well characterised and may be underreported. With the resurgence and continued rise of dengue cases worldwide, physicians must be aware of the less common but serious complications of dengue. Here, we report a patient who presented with severe rhabdomyolysis secondary to dengue fever with a serum creatine kinase of 742 900 U/L.

  16. Meningitis as a primary presentation of Dengue infection

    OpenAIRE

    Bhat, Ramesh Y; Chaitanya Varma

    2013-01-01

    Dengue fever is the most prevalent arboviral infection in the world that is transmitted by mosquitoes. It is an acuteillness of sudden onset that usually follows a benign course with symptoms such as headache, fever and rash. Centralnervous system manifestations of dengue infection are usually rare. Here, a Dengue case with meningitis as primarymanifestation has been presented. J Microbiol Infect Dis 2013; 3(1): 39-40Key words: Meningitis, presentation, Dengue

  17. Current perspectives on the spread of dengue in India

    OpenAIRE

    Gupta E; Ballani N

    2014-01-01

    Ekta Gupta, Neha Ballani Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, IndiaAbstract: Dengue fever (DF) and dengue hemorrhagic fever (DHF) are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with DHF, mainly in Southeast Asia. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. The first major DHF outbreak in the ent...

  18. Dengue: the risk to developed and developing countries.

    OpenAIRE

    Monath, T P

    1994-01-01

    Dengue viruses are members of the Flaviviridae, transmitted principally in a cycle involving humans and mosquito vectors. In the last 20 years the incidence of dengue fever epidemics has increased and hyperendemic transmission has been established over a geographically expanding area. A severe form, dengue hemorrhagic fever (DHF), is an immunopathologic disease occurring in persons who experience sequential dengue infections. The risk of sequential infections, and consequently the incidence o...

  19. Severe Thrombotic Events Associated with Dengue Fever, Brazil

    OpenAIRE

    da Costa, Paulo Sérgio Gonçalves; Ribeiro, Geyza Machado; Junior, Cleber Soares; da Costa Campos, Lenilton

    2012-01-01

    Dengue fever has been a major problem in hospital settings in Brazil for the past 15 years. The main concern has been the severe forms, i.e., dengue hemorrhagic fever and dengue shock syndrome. Hemorrhagic events of different degrees have also been a major concern. We report five cases of large vein thrombotic events associated with the acute phase of dengue fever, including a previously non-reported case of mesenteric vein thrombosis. Complications such as these could have been overlooked in...

  20. Effect of vitamin E on thrombocytopenia in dengue fever

    OpenAIRE

    Arvind Vaish; Sudhir Verma; Abhishek Agarwal; Lokesh Gupta; Manish Gutch

    2012-01-01

    Context: Dengue fever frequently causes thrombocytopenia for which there is no satisfactory treatment. Aim: To evaluate the effect of vitamin E on thrombocytopenia in dengue fever. Settings and Design: A tertiary teaching hospital during a recent outbreak of dengue fever in the area. Materials and Methods: Patients of dengue fever (as per WHO criteria) with thrombocytopenia and platelet counts between 10 × 10 3 /mm 3 and 100 × 10 3 /mm 3 seen during September 1, 2010 to November 30, 2010 were...

  1. All Serotypes of Dengue Viruses Circulating in Kuala Lumpur, Malaysia

    OpenAIRE

    M.H. Chew; Rahman, M. M.; J. Jelip; M. R. Hassan; Isahak, I.

    2012-01-01

    Dengue is a severe disease caused by dengue virus (DENV), transmitted to human being by infected Aedes mosquitoes. It is a major public health concern in Southeast Asia due to its fatality in the form of hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The objective of the study was to isolate and identify dengue virus serotypes prevalent in endemic areas of Kuala Lumpur and Selangor in Malaysia by virus culture, indirect immunoflurecent assay and molecular techniques. A total number ...

  2. Dengue virus type 1 clade replacement in recurring homotypic outbreaks

    OpenAIRE

    Teoh, Boon-Teong; Sam, Sing-Sin; Tan, Kim-Kee; Johari, Jefree; Shu, Meng-Hooi; Danlami, Mohammed Bashar; Abd-Jamil, Juraina; MatRahim, NorAziyah; Mahadi, Nor Muhammad; AbuBakar, Sazaly

    2013-01-01

    Background Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control. Results We used a set of viral envelope (E) gene to reconstruct the phylogeny of DENV-1 isolated between the p...

  3. Molecular epidemiology of dengue viruses from complete genome sequences

    OpenAIRE

    Ong, Swee Hoe

    2010-01-01

    The availability of the complete genetic blueprint of the dengue virus is essential in molecular epidemiological studies to uncover the role of the virus in dengue pathogenesis. During the course of this project, over two hundred complete genomes of the dengue virus were generated from clinical samples collected in three dengue-endemic Southeast Asian countries. In addition, a bioinformatics platform integrating a sequence database, sequence retrieval tools, sequence annotation data and a var...

  4. Epidemiologic update of dengue in the Western Pacific Region, 2010

    OpenAIRE

    Arima, Yuzo; Matsui, Tamano

    2011-01-01

    Dengue is an emerging vectorborne infectious disease that is a major public health concern in the Asia Pacific region. Official dengue surveillance data for 2010 provided by ministries of health were summarized as part of routine activities of the World Health Organization Regional Office for the Western Pacific. Based on reported data, dengue has continued to show an increasing trend in the Western Pacific Region. In 2010, countries and areas reported a total of 353 907 dengue cases, of whic...

  5. Development of ASSURE® dengue IgA rapid test for the detection of anti-dengue IgA from dengue infected patients

    Directory of Open Access Journals (Sweden)

    Yun Ying Tan

    2011-01-01

    Full Text Available Background: Rapid and early dengue diagnosis is essential for patient management and early disease intervention. MP Diagnostics ASSURE® Dengue IgA Rapid Test (Dengue IgA RT was developed for the rapid detection of anti-dengue IgA in patients′ biological samples. The performance of Dengue IgA RT was examined using multiple categories of well-characterized samples. Materials and Methods: Dengue IgA RT was designed and developed. Following characterization of samples by reference ELISAs, the performance of the kit was evaluated. Results: The overall sensitivity and specificity of Dengue IgA RT were 86.70% (n=233 and 86.05% (n=681 respectively; in which Dengue IgA RT detected 77.42% primary and 92.86% secondary cases; compared to 70.97% and 72.14% by IgM-Cap ELISA and 89.25% and 20% by Non-Structural Protein 1 (NS1 Ag ELISA respectively. Using 125 paired samples, Dengue IgA RT showed 84.80% sensitivity at acute phase and 99.20% sensitivity at convalescent phase; with 92% specificity at both phases. Dengue IgA RT also demonstrated a consistent performance (sensitivity: 85.53%, specificity: 80% with 76 whole blood samples. In detecting all four serotypes of DENV (n=162, the performance of Dengue IgA RT was comparable with in-house IgM-Cap ELISA. Kinetics of anti-dengue IgA production was elucidated with 42.86% detection level as early as one-two days after fever onset, which increased to 83.33% between five and seven days after fever onset. Conclusion: Dengue IgA RT demonstrated a good performance and is applicable as one of the dengue early diagnostic tools at all levels of health care system.

  6. Describing dengue epidemics: Insights from simple mechanistic models

    Science.gov (United States)

    Aguiar, Maíra; Stollenwerk, Nico; Kooi, Bob W.

    2012-09-01

    We present a set of nested models to be applied to dengue fever epidemiology. We perform a qualitative study in order to show how much complexity we really need to add into epidemiological models to be able to describe the fluctuations observed in empirical dengue hemorrhagic fever incidence data offering a promising perspective on inference of parameter values from dengue case notifications.

  7. Current perspectives on the spread of dengue in India

    Directory of Open Access Journals (Sweden)

    Gupta E

    2014-12-01

    Full Text Available Ekta Gupta, Neha Ballani Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, IndiaAbstract: Dengue fever (DF and dengue hemorrhagic fever (DHF are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with DHF, mainly in Southeast Asia. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. The first major DHF outbreak in the entire nation occurred in 1996 by dengue virus serotype 2, and after a gap of almost a decade, the country faced yet another DF outbreak in the year 2003 by dengue virus serotype 3. A dramatic increase in the number and frequency of outbreaks followed, and, at present, in most of the states of India, dengue is almost endemic. At present, all the four serotypes are seen in circulation, but the predominant serotype keeps changing. Despite this trend, surveillance, reporting, and diagnosis of dengue remain largely passive in India. More active community-based epidemiological studies with intensive vector control and initiatives for dengue vaccine development should be geared up to control the spread of dengue in India. We review here the factors that may have contributed to the changing epidemiology of dengue in India.Keywords: dengue, epidemiology, India, pathogenesis, vaccine

  8. Reemergence and Autochthonous Transmission of Dengue Virus, Eastern China, 2014.

    Science.gov (United States)

    Wang, Wen; Yu, Bin; Lin, Xian-Dan; Kong, De-Guang; Wang, Jian; Tian, Jun-Hua; Li, Ming-Hui; Holmes, Edward C; Zhang, Yong-Zhen

    2015-09-01

    In 2014, 20 dengue cases were reported in the cities of Wenzhou (5 cases) and Wuhan (15 cases), China, where dengue has rarely been reported. Dengue virus 1 was detected in 4 patients. Although most of these cases were likely imported, epidemiologic analysis provided evidence for autochthonous transmission.

  9. Femoral compressive neuropathy from iliopsoas haematoma complicating dengue hemorrhagic fever

    Institute of Scientific and Technical Information of China (English)

    Sneha Ganu; Yesha Mehta

    2013-01-01

    Dengue fever is a debilitating mosquito-borne disease caused by dengue virus. We reported a case of femoral compression neuropathy due to iliopsoas hematoma complicating dengue hemorrhagic fever. Iliopsoas muscle hematoma can cause femoral neuropathy with resultant pain and paralysis. Such manifestations are not well documented in the literature. The pathogenesis of hematoma and compressive neuropathy with its appropriate management is discussed.

  10. Immature dengue virus : functional properties and potential contribution to disease

    NARCIS (Netherlands)

    Da Silva-Voorham, Júlia Maria

    2013-01-01

    Beter inzicht in mechanismen achter infectieziekte dengue Dengue (‘knokkelkoorts’) is een veelvoorkomende, tropische infectieziekte die wordt overgebracht door muggen. Naar schatting raken jaarlijks zo’n vijftig tot honderd miljoen mensen besmet. Meestal gaat dengue vanzelf over, maar in zo’n 500.00

  11. Concurrent malaria and dengue infection: a brief summary and comment

    OpenAIRE

    Wiwanitkit, Viroj

    2011-01-01

    There are several tropical mosquito borne infections. Malaria and dengue are the two common mosquito infections that are very important and cause high morbidity and mortality for many patients around the world. Concurrent malaria and dengue infection is an important condition that is seldom reported. In this specific article, the author hereby summarizes on the topic of concurrent malaria and dengue infection.

  12. Retinal Hemorrhages in 4 Patients with Dengue Fever

    OpenAIRE

    Chlebicki, Maciej Piotr; Ang, Brenda; Barkham, Timothy; Laude, Augustinus

    2005-01-01

    We report 4 patients with retinal hemorrhages that developed during hospitalization for dengue fever. Onset of symptoms coincided with resolution of fever and the nadir of thrombocytopenia. Retinal hemorrhages may reflect the rising incidence of dengue in Singapore or may be caused by changes in the predominant serotype of the dengue virus.

  13. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

    Directory of Open Access Journals (Sweden)

    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  14. Fight against dengue in India: progresses and challenges.

    Science.gov (United States)

    Gupta, Bhavna; Reddy, B P Niranjan

    2013-04-01

    At the end of the last century, India has faced resurgence of many infectious diseases, of which dengue is one of the most important in terms of morbidity and mortality. The National Vector Borne Disease Control Program data show that dengue is established in India and is becoming endemic to many areas (dengue cases have increased steadily from ∼450 to ∼50,000 from 2000 to 2012). Despite extensive efforts being made in developing the effective dengue control measures, the number of dengue cases, their severity, and geographical boundaries are expanding alarmingly and posing dengue as one of the deadly disease. Recently, the increasing burden of dengue in the country has attracted the scientific as well as Indian Government's administrative attention; however, a lot remain to be achieved for managing the disease under threshold level. Like other vector-borne diseases, better management of the dengue needs balanced approach involving various aspects like disease prevention, cure/treatment, and the vector control, simultaneously. We have briefly discussed here the situation of dengue in India and have tried to highlight the worrying facets of dengue control and its implementation in Indian perspective. The review on various aspects of dengue control has revealed an urgent need for permanent surveillance programs, coupled with improvised disease diagnostics, effective anti-dengue treatment measures, and controlling the disease transmission by following an effective implementation of vector control programs.

  15. Upward Trend in Dengue Incidence among Hospitalized Patients, United States

    OpenAIRE

    Streit, Judy A.; Yang, Ming; Cavanaugh, Joseph E.; Philip M Polgreen

    2011-01-01

    International travel and a global expansion of dengue fever have the potential to increase the incidence of dengue in the United States. We conducted a retrospective cohort analysis of trends in dengue among hospitalized patients by using the National Inpatient Sample (2000–2007); the number of cases more than tripled (p

  16. Upward trend in dengue incidence among hospitalized patients, United States.

    Science.gov (United States)

    Streit, Judy A; Yang, Ming; Cavanaugh, Joseph E; Polgreen, Philip M

    2011-05-01

    International travel and a global expansion of dengue fever have the potential to increase the incidence of dengue in the United States. We conducted a retrospective cohort analysis of trends in dengue among hospitalized patients by using the National Inpatient Sample (2000-2007); the number of cases more than tripled (p<0.0001). PMID:21529411

  17. Serum Aminotransferases in Thai Children With Dengue Infection

    OpenAIRE

    Olarn Prommalikit; Usa Thisyakorn; Chule Thisyakorn

    2015-01-01

    Background: Hepatic manifestations are one of the unusual manifestations of dengue infection. Objectives: We conducted this study in order to study the pattern of serum aminotransferases and sequential changes before and after shock in Thai children with dengue infection. Patients and Methods: Children who were clinically and serologically diagnosed as dengue infection and were adm...

  18. γδ T cell-mediated antibody-dependent cellular cytotoxicity with CD19 antibodies assessed by an impedance-based label-free real-time cytotoxicity assay

    OpenAIRE

    Ursula Jördis Eva Seidel; Fabian eVogt; Ludger eGrosse-Hovest; Gundram eJung; Rupert eHandgretinger; Peter eLang

    2014-01-01

    γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation (SCT) strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) with monoclonal antibodies (mAbs). These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL). To evaluate combination of human γδ T ce...

  19. γδ T Cell-Mediated Antibody-Dependent Cellular Cytotoxicity with CD19 Antibodies Assessed by an Impedance-Based Label-Free Real-Time Cytotoxicity Assay

    OpenAIRE

    Seidel, Ursula Jördis Eva; Vogt, Fabian; Grosse-Hovest, Ludger; Jung, Gundram; Handgretinger, Rupert; Lang, Peter

    2014-01-01

    γδ T cells are not MHC restricted, elicit cytotoxicity against various malignancies, are present in early post-transplant phases in novel stem cell transplantation strategies and have been shown to mediate antibody-dependent cellular cytotoxicity (ADCC) with monoclonal antibodies (mAbs). These features make γδ T cells promising effector cells for antibody-based immunotherapy in pediatric patients with B-lineage acute lymphoblastic leukemia (ALL). To evaluate combination of human γδ T cells wi...

  20. Eventual Role of Asymptomatic Cases of Dengue for the Introduction and Spread of Dengue Viruses in Non-Endemic Regions

    OpenAIRE

    Claude eChastel

    2012-01-01

    In dengue virus infections the asymptomatic cases are much more frequent than the symptomatic ones, but their true role in the introduction and subsequent spread of dengue viruses in non-endemic regions remains to de clarified. We analysed data from English and French literatures to assess if viraemia in asymptomatic dengue infections might be sufficient to represent a true risk. During outbreaks of dengue a large number of individuals are infected and since viraemia levels in symptomatic pa...

  1. Dengue viremia in blood donors in Northern India: Challenges of emerging dengue outbreaks to blood transfusion safety

    OpenAIRE

    Sadhana Mangwana

    2015-01-01

    Backdround: Emerging infectious diseases pose threats to the general human population; including recipients of blood transfusions. Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. Screening blood for dengue antigens in dengue-endemic countries would be costly and should, therefore, be recommended only after careful assessment of risk for infection and cost. Aim: A prospective study was conducted to establish the magnitude of the threat that dengue pos...

  2. 139 Dengue vector control: critical needs and opportunities for helping to control the dengue pandemic

    OpenAIRE

    beaty, barry

    2014-01-01

    Aedes aegypti mosquito control is currently the only option for controlling and preventing epidemic dengue and dengue hemorrhagic fever. However, current approaches for vector control are not stemming the rising tide of dengue disease throughout the tropical world. In the absence of a vaccine, new and effective approaches are needed to improve vector control. Novel approaches to prevent dengue virus transmission will be described and discussed, including (1) the Casa Segura approach to preven...

  3. Clinico-laboratory spectrum of dengue viral infection and risk factors associated with dengue hemorrhagic fever: a retrospective study

    OpenAIRE

    Mallhi, Tauqeer Hussain; Khan, Amer Hayat; Adnan, Azreen Syazril; SARRIFF, Azmi; Khan, Yusra Habib; Jummaat, Fauziah

    2015-01-01

    Background The incidence of dengue is rising steadily in Malaysia since the first major outbreak in 1973. Despite aggressive measures taken by the relevant authorities, Malaysia is still facing worsening dengue crisis over the past few years. There is an urgent need to evaluate dengue cases for better understanding of clinic-laboratory spectrum in order to combat this disease. Methods A retrospective analysis of dengue patients admitted to a tertiary care teaching hospital during the period o...

  4. Concurrent infections by all four dengue virus serotypes during an outbreak of dengue in 2006 in Delhi, India

    Directory of Open Access Journals (Sweden)

    Guleria Randeep

    2008-01-01

    Full Text Available Abstract Background Co-circulation of multiple dengue virus serotypes has been reported from many parts of the world including India, however concurrent infection with more than one serotype of dengue viruses in the same individual is rarely documented. An outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS occurred in and around Delhi in 2006. This is the first report from India with high percentage of concurrent infections with different dengue virus serotypes circulating during one outbreak. Results Acute phase sera from patients were tested for the presence of dengue virus RNA by RT-PCR assay. Of the 69 samples tested for dengue virus RNA, 48 (69.5% were found to be positive. All the four dengue virus serotypes were found to be co-circulating in this outbreak with DENV-3 being the predominant serotype. In addition in 9 of 48 (19% dengue virus positive samples, concurrent infection with more than one dengue virus serotype were identified. Conclusion This is the first report in which concurrent infections with different dengue virus serotypes is being reported during an outbreak from India. Delhi is now truly hyperendemic for dengue.

  5. A role for vector control in dengue vaccine programs.

    Science.gov (United States)

    Christofferson, Rebecca C; Mores, Christopher N

    2015-12-10

    Development and deployment of a successful dengue virus (DENV) vaccine has confounded research and pharmaceutical entities owing to the complex nature of DENV immunity and concerns over exacerbating the risk of DENV hemorrhagic fever (DHF) as a consequence of vaccination. Thus, consensus is growing that a combination of mitigation strategies will be needed for DENV to be successfully controlled, likely involving some form of vector control to enhance a vaccine program. We present here a deterministic compartmental model to illustrate that vector control may enhance vaccination campaigns with imperfect coverage and efficacy. Though we recognize the costs and challenges associated with continuous control programs, simultaneous application of vector control methods coincident with vaccine roll out can have a positive effect by further reducing the number of human cases. The success of such an integrative strategy is predicated on closing gaps in our understanding of the DENV transmission cycle in hyperedemic locations.

  6. A role for vector control in dengue vaccine programs.

    Science.gov (United States)

    Christofferson, Rebecca C; Mores, Christopher N

    2015-12-10

    Development and deployment of a successful dengue virus (DENV) vaccine has confounded research and pharmaceutical entities owing to the complex nature of DENV immunity and concerns over exacerbating the risk of DENV hemorrhagic fever (DHF) as a consequence of vaccination. Thus, consensus is growing that a combination of mitigation strategies will be needed for DENV to be successfully controlled, likely involving some form of vector control to enhance a vaccine program. We present here a deterministic compartmental model to illustrate that vector control may enhance vaccination campaigns with imperfect coverage and efficacy. Though we recognize the costs and challenges associated with continuous control programs, simultaneous application of vector control methods coincident with vaccine roll out can have a positive effect by further reducing the number of human cases. The success of such an integrative strategy is predicated on closing gaps in our understanding of the DENV transmission cycle in hyperedemic locations. PMID:26478199

  7. Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore.

    Science.gov (United States)

    Gan, Victor C; Tan, Li-Kiang; Lye, David C; Pok, Kwoon-Yong; Mok, Shi-Qi; Chua, Rachel Choon-Rong; Leo, Yee-Sin; Ng, Lee-Ching

    2014-01-01

    WHO recommendations for dengue diagnosis require laboratory facilities. Antibody-based rapid diagnostic tests (RDTs) have performed poorly, and clinical diagnosis remains the mainstay in dengue-endemic countries. We evaluated a combination antigen-antibody RDT for point-of-care testing in a high-prevalence setting. In this prospective cohort study, adults were enrolled from a tertiary infectious disease centre for evaluation of undifferentiated febrile illness from October 2011 to May 2012. SD Bioline Dengue Duo was evaluated at point-of-care against a WHO-based reference standard of viral isolation, RT-PCR, NS1-, IgM-, and IgG-ELISA. 246 adults were enrolled (median age 34 years, range 18-69), of which 197 could be confirmed definitively as either dengue or non-dengue. DENV-2 was the predominant serotype (79.5%) and the ratio of primary to secondary cases was 1∶1.1. There were no test failures and minimal interobserver variation with a Fleiss' kappa of 0.983 (95% CI 0.827-1.00). Overall sensitivity and specificity were 93.9% (95% CI 88.8-96.8%) and 92.0% (95% CI 81.2-96.9%) respectively. Using WHO clinical criteria alone for diagnosis had similar sensitivities (95.9%, 95% CI 91.4-98.1%) and lower specificities (20.0%, 95% CI 11.2-33.0%). No significant difference in performance was found when testing early versus late presenters, primary versus secondary cases, or DENV-1 versus DENV-2 infections. The use of a combination RDT fulfills WHO ASSURED criteria for point-of-care testing and can enhance dengue diagnosis in an endemic setting. This has the potential to markedly improve clinical management of dengue in the field.

  8. Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore.

    Directory of Open Access Journals (Sweden)

    Victor C Gan

    Full Text Available WHO recommendations for dengue diagnosis require laboratory facilities. Antibody-based rapid diagnostic tests (RDTs have performed poorly, and clinical diagnosis remains the mainstay in dengue-endemic countries. We evaluated a combination antigen-antibody RDT for point-of-care testing in a high-prevalence setting. In this prospective cohort study, adults were enrolled from a tertiary infectious disease centre for evaluation of undifferentiated febrile illness from October 2011 to May 2012. SD Bioline Dengue Duo was evaluated at point-of-care against a WHO-based reference standard of viral isolation, RT-PCR, NS1-, IgM-, and IgG-ELISA. 246 adults were enrolled (median age 34 years, range 18-69, of which 197 could be confirmed definitively as either dengue or non-dengue. DENV-2 was the predominant serotype (79.5% and the ratio of primary to secondary cases was 1∶1.1. There were no test failures and minimal interobserver variation with a Fleiss' kappa of 0.983 (95% CI 0.827-1.00. Overall sensitivity and specificity were 93.9% (95% CI 88.8-96.8% and 92.0% (95% CI 81.2-96.9% respectively. Using WHO clinical criteria alone for diagnosis had similar sensitivities (95.9%, 95% CI 91.4-98.1% and lower specificities (20.0%, 95% CI 11.2-33.0%. No significant difference in performance was found when testing early versus late presenters, primary versus secondary cases, or DENV-1 versus DENV-2 infections. The use of a combination RDT fulfills WHO ASSURED criteria for point-of-care testing and can enhance dengue diagnosis in an endemic setting. This has the potential to markedly improve clinical management of dengue in the field.

  9. Epidemiological update on the dengue situation in the Western Pacific Region, 2012

    Directory of Open Access Journals (Sweden)

    Yuzo Arima

    2015-04-01

    Full Text Available Dengue has caused a substantial public health burden in the Western Pacific Region. To assess this burden and regional trends, data were collated and summarized from indicator-based surveillance systems on dengue cases and deaths from countries and areas in the Western Pacific Region. In 2012, dengue notifications continued to increase with 356 838 dengue cases reported in the Region (relative to 244 855 cases reported in 2011 of which 1248 died. In the Asia subregion, the notification rate was highest in Cambodia, the Philippines and the Lao People’s Democratic Republic (316.2, 198.9 and 162.4 per 100 000 population, respectively, and in the Pacific island countries and areas, the notification rate was highest in Niue, the Marshall Islands and the Federated States of Micronesia (8556.0, 337.0 and 265.1 per 100 000 population, respectively. All four serotypes were circulating in the Region in 2012 with considerable variabilitiy in distribution. Regional surveillance provides important information to enhance situational awareness, conduct risk assessments and improve preparedness activities.

  10. Epidemiology of dengue: past, present and future prospects.

    Science.gov (United States)

    Murray, Natasha Evelyn Anne; Quam, Mikkel B; Wilder-Smith, Annelies

    2013-01-01

    Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265-420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012-2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective of

  11. Epidemiology of dengue: past, present and future prospects.

    Science.gov (United States)

    Murray, Natasha Evelyn Anne; Quam, Mikkel B; Wilder-Smith, Annelies

    2013-01-01

    Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265-420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012-2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective of

  12. Neuralgic amyotrophy associated with dengue fever: Case series of three patients

    Directory of Open Access Journals (Sweden)

    R Verma

    2011-01-01

    Full Text Available Dengue is an acute mosquito borne viral infection caused by one of the four distinct serotype of dengue viruses (type 1-4, belonging to flavivirus family. Dengue fever, an arboviral infection is known to cause various neurological complications. Commonly reported neurological manifestations associated with dengue infection are encephalopathy, myelopathy, stroke, Guillain-Barre syndrome and hypokalemic paralysis. Brachial amyotrophy associated with dengue infection were not described previously. Here, we describe three patients presenting with brachial neuritis associated with dengue infection. Dengue infection should be considered in the etiological list of brachial neuritis in dengue endemic areas, especially if preceded by history of febrile illness compatible with dengue illness.

  13. Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

  14. Profile of hepatic involvement by dengue virus in dengue infected children

    Directory of Open Access Journals (Sweden)

    Amrita Roy

    2013-01-01

    Full Text Available Background: The spectrum of liver dysfunction in children with dengue infection is wide and has been associated with disease severity. Aims: This study was undertaken to estimate the range of hepatic involvement in dengue infection in children. Materials and Methods: This study assessed the biochemical and clinical profile of hepatic involvement by dengue virus in 120 children with serologically positive dengue fever (DF, aged 2 months to 14 years. Results: All cases were grouped into DF without warning signs (Group 1, DF with warning signs (Group 2 and severe dengue (Group 3 according to revised World Health Organization 2009 criteria. The spectrum of hepatic manifestations included hepatomegaly (80.8%, hepatic tenderness (46.3%, jaundice (60%, raised aspartate transaminase (AST, alanine transaminase (ALT and prolonged prothrombin time (41.7% and reduced serum albumin (56%. Conclusions: Hepatic dysfunction was observed more in Groups 2 and 3. There was 84.4% and 93.75% ALT and AST elevation respectively in Group 2 and 94.5% and 95.9% ALT and AST elevation respectively in Group 3 and fulminant hepatic failure was observed in Group 3. Therefore in a child with fever, jaundice, hepatomegaly and altered liver function tests, the diagnosis of dengue infection should be strongly considered in areas where dengue infection is endemic.

  15. Clinically profiling pediatric patients with dengue

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    Sriram Pothapregada

    2016-01-01

    Full Text Available Objective: To study the clinical profile and outcome of dengue fever in children at a tertiary care hospital in Puducherry. Materials and Methods: All children (0-12 years of age diagnosed and confirmed as dengue fever from August 2012 to January 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies, and the data were analyzed using SPSS 16.0 statistical software. After collecting the data, all the variables were summarized by descriptive statistics. Results: Among the 261 confirmed cases of dengue fever non-severe and severe dengue infection was seen in 60.9% and 39.1%, respectively. The mean age (standard deviation of the presentation was 6.9 + 3.3 years and male: female ratio was 1.2:1. The most common clinical manifestations were fever (94.6%, conjunctival congestion (89.6%, myalgia (81.9%, coryza (79.7%, headache (75.1%, palmar erythema (62.8%, and retro-orbital pain (51.3%. The common early warning signs at the time of admission were persistent vomiting (75.1%, liver enlargement (59.8%, cold and clammy extremities (45.2%, pain abdomen (31.0%, hypotension (29.5%, restlessness (26.4%, giddiness (23.0%, bleeding (19.9%, and oliguria (18.4%. The common manifestation of severe dengue infection was shock (39.1%, bleeding (19.9%, and multi-organ dysfunction (2.3%. The most common complications were liver dysfunction, acute respiratory distress syndrome, encephalopathy, pleural effusion, ascites, myocarditis, myositis, acute kidney injury, and disseminated intravascular coagulopathy. Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.3% and out of them four presented with impaired consciousness (66.6%. The common causes for poor outcome were multiorgan failure, encephalopathy, and fluid refractory shock

  16. Imunocompetent Mice Model for Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves

    2012-01-01

    Full Text Available Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV. DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

  17. Autoimmune pathogenesis in dengue virus infection.

    Science.gov (United States)

    Lin, Chiou-Feng; Wan, Shu-Wen; Cheng, Hsien-Jen; Lei, Huan-Yao; Lin, Yee-Shin

    2006-01-01

    The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) caused by dengue virus (DV) infection remain unresolved. Patients with DHF/DSS are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and hepatomegaly. In addition to the effect of virus load and virus variation, abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS. Actually, viral autoimmunity is involved in the pathogenesis of numerous viral infections, such as human immunodeficiency virus, human hepatitis C virus, human cytomegalovirus, herpes simplex virus, Epstein- Barr virus, and DV. In this review, we discuss the implications of autoimmunity in dengue pathogenesis. Antibodies directed against DV nonstructural protein 1 (NS1) showed cross-reactivity with human platelets and endothelial cells, which lead to platelet and endothelial cell damage and inflammatory activation. Based on these findings, we hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development.

  18. Dengue: muscle biopsy findings in 15 patients

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    S.M.F. Malheiros

    1993-06-01

    Full Text Available Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry in 15 patients (4 males, median age 23 years (range 14-47 with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

  19. First Iranian imported case of dengue

    Directory of Open Access Journals (Sweden)

    Masoud Mardani

    2013-01-01

    Full Text Available Dengue fever, a mosquito-borne flavivirus infection, is endemic in Southeast Asia. Currently, incidences have been increasing among adults. There have been no published reports of dengue fever from Iran. Widespread connection between different countries may predispose them for acquisition of infection. The patient was a 58-year-old Iranian woman with acute unexplained high-grade fever for 4 days, associated with skin rash, after returning from Southeast Asia. CBC showed WBC = 1600/mm 3 and platelet count 99,000/mm 3 . The patient also had hematuria. ELISA immunoglobulin M (IgM antibodies to dengue and serum RT-PCR for dengue virus was positive. The patient managed with conservative treatment and due to good general condition and improvement specific antiviral treatment was not started. She became afebrile at the 3 rd day of hospitalization and discharged with good general condition on fourth day. She was afebrile after two weeks follow-up. Dengue fever has been increasing among adults. It should be suspected, when a patient presents with acute febrile illness and skin rashes returning from endemic region. Conservative treatment may be conducted in uncomplicated cases .

  20. Dengue Surveillance in Veterans Affairs Healthcare Facilities, 2007–2010

    OpenAIRE

    Patricia L Schirmer; Lucero-Obusan, Cynthia A.; Benoit, Stephen R.; Santiago, Luis M.; Danielle Stanek; Achintya Dey; Mirsonia Martinez; Gina Oda; Mark Holodniy

    2013-01-01

    BACKGROUND: Although dengue is endemic in Puerto Rico (PR), 2007 and 2010 were recognized as epidemic years. In the continental United States (US), outside of the Texas-Mexico border, there had not been a dengue outbreak since 1946 until dengue re-emerged in Key West, Florida (FL), in 2009-2010. The objective of this study was to use electronic and manual surveillance systems to identify dengue cases in Veterans Affairs (VA) healthcare facilities and then to clinically compare dengue cases in...

  1. Understanding the relative importance of global dengue risk factors.

    Science.gov (United States)

    Lowe, Rachel

    2015-10-01

    Dengue is a mosquito-transmitted viral infection of major international public health concern. Global environmental and socio-economic change has created ideal conditions for the global expansion of dengue transmission. Innovative modelling tools help in understanding the global determinants of dengue risk and the relative impact of environmental and socio-economic factors on dengue transmission and spread. While climatic factors may act as a limiting factor on the global scale, other processes may play a dominant role at the local level. Understanding the spatial scales at which environmental and socio-economic factors dominate can help to target appropriate dengue control and prevention strategies. PMID:26311416

  2. Gravitraps for management of dengue clusters in Singapore.

    Science.gov (United States)

    Lee, Caleb; Vythilingam, Indra; Chong, Chee-Seng; Abdul Razak, Muhammad Aliff; Tan, Cheong-Huat; Liew, Christina; Pok, Kwoon-Yong; Ng, Lee-Ching

    2013-05-01

    Although Singapore has an intensive dengue control program, dengue remains endemic with regular outbreaks. We report development and use of a novel adult oviposition trap, the Gravitrap, in managing dengue cluster areas. The Gravitrap is a simple, hay infusion-filled cylindrical trap with a sticky inner surface to serve as an oviposition site for gravid female Aedes mosquitoes. Wire gauze fitted above the water level minimizes the risk of it being an unwanted breeding habitat. The Gravitrap was deployed in 11 dengue cluster areas throughout Singapore. Aedes aegypti was the predominant mosquito caught in the trap and some (5.73%) were found to be positive for dengue virus.

  3. Cost of Dengue Vector Control Activities in Malaysia

    OpenAIRE

    Packierisamy, P. Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K.; Halasa, Yara A.; Donald S Shepard

    2015-01-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Con...

  4. Severe Dengue Virus Infection in Pediatric Travelers Visiting Friends and Relatives after Travel to the Caribbean

    OpenAIRE

    Krishnan, Nivedita; Purswani, Murli; Hagmann, Stefan

    2012-01-01

    Of eight children given a diagnosis of dengue, a complicated course developed in three (38%), including one infant with dengue shock syndrome. Children visiting friends and relatives in dengue-endemic regions are at risk for severe dengue-associated morbidity. Children of families originally from these locations may benefit from pre-travel advice and may represent candidates for a future dengue vaccine.

  5. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ... affected. Before 1970 only nine countries had experienced Dengue Hemorrhagic Fever (DHF) epidemics, a... means for prevention of dengue infection and dengue hemorrhagic fever (DHF) by immunization with... Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,...

  6. Trends of dengue infections in Malaysia, 2000-2010

    Institute of Scientific and Technical Information of China (English)

    Md Shahin Mia; Rawshan Ara Begum; AC Er; Joy Jacqueline Pereira

    2013-01-01

    Objective: To analyze trends of dengue incidences and deaths in Malaysia from 2000 to 2010 as well as the predominant dengue virus serotypes during the last decade. Methods: We used the national data on annual reported cases, deaths, incidence rate, mortality rate, and case fatality rate of dengue fever (DF) and dengue hemorrhagic fever (DHF) as well as dengue virus serotypes prevalent in Malaysia during the last decade. Trend/ regression lines were fitted to investigate the trend of dengue incidences and deaths due to the disease for a 11-year period (2000-2010). For the distribution of national incidence rate, mortality rate, and case fatality rate of DF and DHF, descriptive statistics using mean and 95% confidence intervals (CI) for means, and range were applied. Results: The number of dengue cases and number of deaths have increased, on average, by 14% and 8% per year respectively. The average annual incidence rate of DF per 100 000 populations was higher as compared to that of DHF. Conversely, the yearly mean mortality rate of DHF per 100 000 populations was greater than that of DF. The simultaneous circulation of all four dengue serotypes has been found in Malaysia. But a particular dengue virus serotype predominates for at least two years before it becomes replaced by another serotype. Conclusions:The dengue situation in Malaysia has worsened with an increasing number of reported cases and deaths during the last decade. The increasing trend of dengue highlights the need for a more systematic surveillance and reporting of the disease.

  7. Concurrent dengue and malaria in an area in Kolkata

    Institute of Scientific and Technical Information of China (English)

    Amiya Kumar Hati; Indranil Bhattacharjee; Hiranmoy Mukherjee; Bhaswati Bandyopadhayay; Deban Bandyopadhyay; Rajyasree De; Goutam Chandra

    2012-01-01

    ABSTRACT Objective:To establish the nature and extent of dual dengue and malaria infections in an endemic area through a longitudinal study.Methods: A prospective study was conducted from August2005to December2010to document the nature and extent of concurrent dengue and malaria infections in an area in central Kolkata, endemic both for dengue and malaria.Results:Of2 971 suspected cases of dengue fever, in605 (20.36%)persons dengue infection was detected, of whom46 (7.60%, 46/605)patients (40 and6suffered from secondary and primary dengue fever respectively) were simultaneously suffering from malaria (28 and18 were infected with Plasmodium vivax (P.vivax) andPlasmodium falciparum (P. falciparum) respectively, such dual infections of dengue and malaria were detected in all the years of the study period, except 2007, indicating intense transmission of both dengue and malaria in the study area, and the phenomenon was not an isolated one, the rate of concomitant infections ranged from25% in2009 to4.9% in 2005. Out of total population surveyed,1.54% (46/2 971)had concurrent dengue and malaria infection.Conclusions: These findings added a new dimension in diagnosis, treatment, epidemiology and control of dengue and malaria. The possible risk of concurrent dengue and malaria infections should always be kept in mind in endemic areas for early diagnosis employing modern technology and prompt and effective treatment to avoid serious complications.

  8. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

    Directory of Open Access Journals (Sweden)

    Om Parkash

    2015-10-01

    Full Text Available Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed.

  9. Dengue fever presenting as acute liver failure- a case report

    Institute of Scientific and Technical Information of China (English)

    Rajat Jhamb; Bineeta Kashyap; Ranga GS; Kumar A

    2011-01-01

    Dengue fever(DF) and dengue haemorrhagic fever(DHF) are important mosquito-borne viral diseases of humans and recognized as important emerging infectious diseases in the tropics and subtropics. Compared to nine reporting countries in the 1950s, today the geographic distribution includes more than100 countries worldwide. Dengue viral infections are known to present a diverse clinical spectrum, ranging from asymptomatic illness to fatal dengue shock syndrome. Mild hepatic dysfunction in dengue haemorrhagic fever is usual. However, its presentation as acute liver failure(ALF)is unusual. We report a patient with dengue shock syndrome who presented with acute liver failure and hepatic encephalopathy in a recent outbreak of dengue fever in Delhi, India.

  10. Dendritic Cell Apoptosis and the Pathogenesis of Dengue

    Directory of Open Access Journals (Sweden)

    Lysangela R. Alves

    2012-11-01

    Full Text Available Dengue viruses and other members of the Flaviviridae family are emerging human pathogens. Dengue is transmitted to humans by Aedes aegypti female mosquitoes. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. Dendritic cells (DCs are key antigen presenting cells, sensing pathogens, processing and presenting the antigens to T lymphocytes, and triggering an adaptive immune response. Infection of DCs by dengue virus may induce apoptosis, impairing their ability to present antigens to T cells, and thereby contributing to dengue pathogenesis. This review focuses on general mechanisms by which dengue virus triggers apoptosis, and possible influence of DC-apoptosis on dengue disease severity.

  11. Implication of vaccination against dengue for Zika outbreak

    Science.gov (United States)

    Tang, Biao; Xiao, Yanni; Wu, Jianhong

    2016-01-01

    Zika virus co-circulates with dengue in tropical and sub-tropical regions. Cases of co-infection by dengue and Zika have been reported, the implication of this co-infection for an integrated intervention program for controlling both dengue and Zika must be addressed urgently. Here, we formulate a mathematical model to describe the transmission dynamics of co-infection of dengue and Zika with particular focus on the effects of Zika outbreak by vaccination against dengue among human hosts. Our analysis determines specific conditions under which vaccination against dengue can significantly increase the Zika outbreak peak, and speed up the Zika outbreak peak timing. Our results call for further study about the co-infection to direct an integrated control to balance the benefits for dengue control and the damages of Zika outbreak. PMID:27774987

  12. Dengue vaccine: a valuable asset for the future.

    Science.gov (United States)

    Jindal, Harashish; Bhatt, Bhumika; Malik, Jagbir Singh; S K, Shashikantha

    2014-01-01

    Dengue has emerged as one of the major global public health problems. The disease has broken out of its shell and has spread due to increased international travel and climatic changes. Globally, over 2.5 billion people accounting for >40% of the world's population are at risk from dengue. Since the 1940s, dengue vaccines have been under investigation. A live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue virus (CYD-TDV) has progressed to phase III efficacy studies. Dengue vaccine has been found to be a cost-effective intervention to reduce morbidity and mortality. Current dengue vaccine candidates aim to protect against the 4 dengue serotypes, but the recent discovery of a fifth serotype could complicate vaccine development. In recent years, an urgent need has been felt for a vaccine to prevent the morbidity and mortality from this disease in a cost-effective way. PMID:25424928

  13. Real time PCR. Application in dengue studies

    Directory of Open Access Journals (Sweden)

    Jeanette Prada-Arismendy

    2011-06-01

    Full Text Available PCR (polymerase chain reaction is a routinely used tool in every diagnostic and research laboratory. This technique has been used in detection of mutations and pathogens, forensic investigation, and even is the base tool for human genome sequencing. A modification of PCR technique, real time PCR, allows the quantification of nucleic acids with higher sensibility, specificity and reproducibility. This article is intended to clarify the foundations of real-time PCR, using an application model for virology. In the actual work, it was quantified the viral load of dengue virus serotype 2 produced from infected murine macrophages; the obtained results in this work established that murine strain BALB/c presents a greater susceptibility to dengue virus infection, which establishes BALB/c murine strain as a best model of study for investigation of dengue virus infection physiopathology.

  14. Optimal Repellent Usage to Combat Dengue Fever.

    Science.gov (United States)

    Dorsett, Chasity; Oh, Hyunju; Paulemond, Marie Laura; Rychtář, Jan

    2016-05-01

    Dengue fever is one of the most important vector-borne diseases. It is transmitted by Aedes Stegomyia aegypti, and one of the most effective strategies to combat the disease is the reduction of exposure to bites of these mosquitoes. In this paper, we present a game-theoretical model in which individuals choose their own level of protection against mosquito bites in order to maximize their own benefits, effectively balancing the cost of protection and the risk of contracting the dengue fever. We find that even when the usage of protection is strictly voluntary, as soon as the cost of protection is about 10,000 times less than the cost of contracting dengue fever, the optimal level of protection will be within 5 % of the level needed for herd immunity. PMID:27142427

  15. Non-hemorrhagic dengue fever with rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Ratan Jha

    2013-01-01

    Full Text Available Acute kidney injury occurs in 33-50% of patients with rhabdomyolysis and infections remain one of the major contributing factors. The incidence of rhabdomyolysis in non-hemorrhagic dengue virus infection is quite low and may go unnoticed, especially if the presentation is not florid. We report a case of a young male patient, sero-positive for dengue, with no hemorrhagic manifestations or hypotension, who developed rhabdomyolysis complicated by renal failure. The patient eventually needed dialysis support and later recovered fully. Clinicians need to be aware of the occurrence of rhabdomyolysis even in patients without the hemorrhagic manifestations of dengue viral infection and should employ early preventive strategies in such cases.

  16. Dengue virus serotype in Aceh Province

    Directory of Open Access Journals (Sweden)

    Paisal

    2015-06-01

    Full Text Available WHO estimated 50 million dengue infections happen every year in the world. In Indonesia, there were 90,245 DHF cases on 2012 with 816 deaths. In the Province of Aceh, 2,269 cases happened in the same year. This study aimed to identify dengue virus serotype in Aceh. Sampling was done in Kota Banda Aceh Hospital, Kota Lhokseumawe Hospital, Kabupaten Aceh Tamiang Hospital, Kabupaten Aceh Barat Hospital, and Kabupaten Simeulue Hospital between May to December 2012. This was a clinical laboratory research with observation design using cross sectional approach. Research’s population was sample from patients with dengue clinical symptom. Using purposive sampling technique, we have collected 100 samples from the five hospitals (20 samples from each hospital. From RT-PCR, we found 16 positive samples (9 samples were DENV-4, 3 samples were DENV-1, 2 samples were DENV-2, and 2 samples were DENV-3.

  17. Dynamics of Dengue epidemics using optimal control

    CERN Document Server

    Rodrigues, Helena Sofia; Torres, Delfim F M

    2010-01-01

    We present an application of optimal control theory to Dengue epidemics. This epidemiologic disease is an important theme in tropical countries due to the growing number of infected individuals. The dynamic model is described by a set of nonlinear ordinary differential equations, that depend on the dynamic of the Dengue mosquito, the number of infected individuals, and the people's motivation to combat the mosquito. The cost functional depends not only on the costs of medical treatment of the infected people but also on the costs related to educational and sanitary campaigns. Two approaches to solve the problem are considered: one using optimal control theory, another one by discretizing first the problem and then solving it with nonlinear programming. The results obtained with OC-ODE and IPOPT solvers are given and discussed. We observe that with current computational tools it is easy to obtain, in an efficient way, better solutions to Dengue problems, leading to a decrease of infected mosquitoes and individ...

  18. Dengue vaccines: Challenges, development, current status and prospects

    Directory of Open Access Journals (Sweden)

    A Ghosh

    2015-01-01

    Full Text Available Infection with dengue virus (DENV is the most rapidly spreading mosquito-borne viral disease in the world. The clinical spectrum of dengue, caused by any of the four serotypes of DENV, ranges from mild self-limiting dengue fever to severe dengue, in the form dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. Increased rates of hospitalization due to severe dengue, during outbreaks, result in massive economic losses and strained health services. In the absence of specific antiviral therapy, control of transmission of DENV by vector management is the sole method available for decreasing dengue-associated morbidity. Since vector control strategies alone have not been able to satisfactorily achieve reduction in viral transmission, the implementation of a safe, efficacious and cost-effective dengue vaccine as a supplementary measure is a high public health priority. However, the unique and complex immunopathology of dengue has complicated vaccine development. Dengue vaccines have also been challenged by critical issues like lack of animal models for the disease and absence of suitable markers of protective immunity. Although no licensed dengue vaccine is yet available, several vaccine candidates are under phases of development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored vaccines. Although some vaccine candidates have progressed from animal trials to phase II and III in humans, a number of issues regarding implementation of dengue vaccine in countries like India still need to be addressed. Despite the current limitations, collaborative effects of regulatory bodies like World Health Organization with vaccine manufacturers and policy makers, to facilitate vaccine development and standardize field trials can make a safe and efficacious dengue vaccine a reality in near future.

  19. Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries.

    OpenAIRE

    Barniol, J; Gaczkowski, R; Barbato, EV; da Cunha, RV; Salgado, D.; E. Martínez; Segarra, CS; Pleites Sandoval, EB; Mishra, A; Laksono, IS; Lum, LC; Martínez, JG; Núnez, A; Balsameda, A; Allende, I

    2011-01-01

    BACKGROUND: In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems re...

  20. Usefulness and applicability of the revised dengue case classification by disease: multi-centre study in 18 countries

    OpenAIRE

    Villegas Elci; Ooi Eng E; Akbar Naeema A; Thomacheck Kay; Dimaano Efren; Ramírez Gladys; Balsameda Angel; Allende Ivan; Núnez Andrea; Martínez José G; Lum Lucy CS; Laksono Ida; Mishra Ajay; Pleites Sandoval Ernesto B; Segarra Carmita

    2011-01-01

    Abstract Background In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification sy...

  1. Clinical evaluation of dengue RNA, NS1, and IgM for diagnosis of dengue in Southern China.

    Science.gov (United States)

    Chen, Xinliang; Chen, Rui; Gu, Wenshen; He, Jian; Cai, Weipeng; Li, Jiajia; Duan, Chaohui; Yan, Haiyan

    2016-01-01

    In 2014, a large outbreak of dengue occurred in Guangzhou, China. This outbreak prompted us to evaluate NS1 and RNA for the early diagnosis of acute dengue infection, in addition to the combination with IgM antibody. We aimed to find the differences of three assays about dengue diagnosis. This study was an evaluation of diagnosis test. Based on WHO criteria 2009, dengue RNA, NS1, and IgM/IgG were detected from 294 patients (180 dengue patients, 114 non-dengue patients) by three diagnostic kits made in China. The χ(2) test, sensitivity, and specificity were used in statistical analysis. The ratios of dengue patients with low platelet counts (dengue patients (P Dengue NS1 was shown sensitive (93.9%) for diagnostic use. RNA had a better performance with 98.1% of sensitivity from day 1 to day 4 after illness onset. IgM performed better at day 5 or more with 74.0% of sensitivity. The diagnostic rate using a combination of RNA and IgM was 97.8% and 96.7% using NS1 and IgM. A patient with low platelet and white blood cell counts needs additional tests for dengue during an epidemic. RNA and NS1 were most valuable for early diagnosis of dengue, whereas IgM was best suited as a supplementary method for patients at day 5 or more after illness onset.

  2. CpG-A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations

    NARCIS (Netherlands)

    H.H. van Ojik; L. Bevaart; C.E. Dahle; A. Bakker (Annie); M.J.H. Jansen (Marco); M.J. van Vugt; J.G. van de Winkel; G.J. Weiner

    2003-01-01

    textabstractImmunostimulatory CpG oligodeoxynucleotides (ODNs) can enhance the therapeutic effect of monoclonal antibodies (mAbs) by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Distinct classes of CpG ODNs have been found recently to stimulate different effector

  3. Evaluation of the diagnostic accuracy of a new dengue IgA capture assay (Platelia Dengue IgA Capture, Bio-Rad for dengue infection detection.

    Directory of Open Access Journals (Sweden)

    Sophie De Decker

    2015-03-01

    Full Text Available Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, Institut Pasteur in French Guiana were selected among samples collected between 2002 and 2013 from patients exhibiting a dengue-like syndrome. A first group included 134 sera from confirmed dengue-infected patients, and a second included 50 sera from non-dengue infected patients, all collected between day 3 and day 15 after the onset of fever. Dengue infection diagnoses were all confirmed using reference assays by direct virological identification using RT-PCR or virus culture on acute sera samples or on paired acute-phase sera samples of selected convalescent sera. This study revealed: i a good overall sensitivity and specificity of the IgA index test, i.e., 93% and 88% respectively, indicating its good correlation to acute dengue diagnosis; and ii a good concordance with the Panbio IgM capture ELISA. Because of the shorter persistence of dengue virus-specific IgA than IgM, these results underlined the relevance of this new test, which could significantly improve dengue diagnosis accuracy, especially in countries where dengue virus is (hyper- endemic. It would allow for additional refinement of dengue diagnostic strategy.

  4. Evaluation of the diagnostic accuracy of a new dengue IgA capture assay (Platelia Dengue IgA Capture, Bio-Rad) for dengue infection detection.

    Science.gov (United States)

    De Decker, Sophie; Vray, Muriel; Sistek, Viridiana; Labeau, Bhety; Enfissi, Antoine; Rousset, Dominique; Matheus, Séverine

    2015-03-01

    Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, Institut Pasteur in French Guiana) were selected among samples collected between 2002 and 2013 from patients exhibiting a dengue-like syndrome. A first group included 134 sera from confirmed dengue-infected patients, and a second included 50 sera from non-dengue infected patients, all collected between day 3 and day 15 after the onset of fever. Dengue infection diagnoses were all confirmed using reference assays by direct virological identification using RT-PCR or virus culture on acute sera samples or on paired acute-phase sera samples of selected convalescent sera. This study revealed: i) a good overall sensitivity and specificity of the IgA index test, i.e., 93% and 88% respectively, indicating its good correlation to acute dengue diagnosis; and ii) a good concordance with the Panbio IgM capture ELISA. Because of the shorter persistence of dengue virus-specific IgA than IgM, these results underlined the relevance of this new test, which could significantly improve dengue diagnosis accuracy, especially in countries where dengue virus is (hyper-) endemic. It would allow for additional refinement of dengue diagnostic strategy.

  5. Molecular epidemiology of dengue viruses in Brazil

    Directory of Open Access Journals (Sweden)

    Rita Maria Ribeiro Nogueira

    2000-01-01

    Full Text Available Dengue viruses (DEN are found as four antigenically distinct serotypes designated DEN-1, 2, 3, and 4. Laboratory evidence that strain-intratypical variation occurs among DEN viruses has been demonstrated since the 1970s, although only with the advances in molecular technologies has it been possible to determine the genetic variability of each serotype. Genotypical identification has proven to be a useful tool for determining the origin and spread of epidemics and to correlate virulence of strains. In this report we present the results of molecular epidemiological studies with the DEN-1 and DEN-2 viruses that caused dengue epidemics in Brazil during the last decade.

  6. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  7. Aedes mosquito salivary immune peptides:boost or block dengue viral infections

    Institute of Scientific and Technical Information of China (English)

    Natthanej Luplertlop

    2014-01-01

    Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  8. Characterization of the 2013 dengue epidemic in Myanmar with dengue virus 1 as the dominant serotype.

    Science.gov (United States)

    Ngwe Tun, Mya Myat; Kyaw, Aung Kyaw; Makki, Nader; Muthugala, Rohitha; Nabeshima, Takeshi; Inoue, Shingo; Hayasaka, Daisuke; Moi, Meng Ling; Buerano, Corazon C; Thwe, Saw Myat; Thant, Kyaw Zin; Morita, Kouichi

    2016-09-01

    In 2013 in Myanmar, dengue epidemic occurred with 20,255 cases including 84 deaths. This study aimed to determine the serological and molecular characteristics of dengue virus (DENV) infection among children with clinical diagnosis of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) during this period. Single acute serum samples were collected from 300 children in Mandalay Children Hospital, Mandalay, Myanmar. Out of the 300 children, 175 (58.3%) and 183 (61%) were positive for anti-dengue IgM and anti-dengue IgG, respectively. Among the IgM positives, 41 (23.4%) had primary DENV infection. Thirty-nine DENV strains (23 DENV-1, 10 DENV-2 and 6 DENV-4) were successfully isolated after inoculation of the patient serum samples onto C6/36 cells. DENV 1 was the dominant serotype in the 2013 epidemic. There was no correlation between the infecting serotypes and clinical severities. The DENV-1 strains belonged to three lineages of the genotype 1; the DENV-2 strains were of the Asian I genotype and were separated into two lineages; and DENV-4 strains belonged to the same lineage of genotype I. It is of interest to note the diversity of DENV-1 and -2 circulating in the same location during June-August 2013. These DENV isolates were genetically close (98%-100%) to the other previously reported isolates from Myanmar and its neighboring countries, namely China, Thailand, Sri Lanka, Cambodia and Vietnam. Primary DENV infection was still high among the severe dengue cases. Different serotypes of DENV were co-circulating in 2013, however, genotype shift was not observed. Additionally, amino acid mutations were detected in the study strains not seen in the previously reported strains from other countries and Myanmar. This paper provided information on the circulating serotypes for the last 15years and the recent dengue situation in Mandalay, Myanmar after 2006. PMID:27154331

  9. Dengue on islands: a Bayesian approach to understanding the global ecology of dengue viruses

    OpenAIRE

    Feldstein, Leora R.; John S Brownstein; Brady, Oliver J.; Simon I Hay; Johansson, Michael A.

    2015-01-01

    Background: Transmission of dengue viruses (DENV), the most common arboviral pathogens globally, is influenced by many climatic and socioeconomic factors. However, the relative contributions of these factors on a global scale are unclear. Methods: We randomly selected 94 islands stratified by socioeconomic and geographic characteristics. With a Bayesian model, we assessed factors contributing to the probability of islands having a history of any dengue outbreaks and of having frequent outbrea...

  10. Penentuan Serotipe Virus Dengue dan Gambaran Manifestasi Klinis serta Hematologi Rutin pada Infeksi Virus Dengue

    Directory of Open Access Journals (Sweden)

    Basti Andriyoko

    2012-12-01

    Full Text Available All DENV serotypes can cause a spectrum of disease from dengue fever (DF to dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. It is difficult to differentiate clinical characteristicand hematologic result for each serotype. Aim of this study were to determine dengue serotype and describe clinical manifestation of DF, DHF, DSS and routine hematologic results, i.e.haemoglobin, hematocrit, leukocyte, and thrombocyte in each serotype. This study was conducted at Dr. Hasan Sadikin Hospital Bandung from March 2010 until July 2011. Subjects were dengue patients aged >14 years with a history of fever <5 days. Blood samples were taken for serotype determination by reverse transcription polymerase chain reaction (RT-PCR followed by semi-nested PCR. Clinical manifestation data and haematologic result were obtained from medical records. This was a descriptive study. Seventy five patients were included in this study. Dengue serotype can be detected in 27 (36% samples with DENV-3 (13 were dominating followed by DENV-2 (8, DENV-4 (4, and DENV-1 (2. DHF was mainly found in DENV-3. DENV-2 gavethe highest decrease in hemoglobin, highest percentage increase in haematocrit, lowest leukocyte, and lowest thrombocyte. In conclusion, all 4 serotypes are found in RSUP Dr. Hasan Sadikin Hospital Bandung with DENV-3 domination. DHF is mainly caused by DENV-3.

  11. Commercial Dengue Rapid Diagnostic Tests for Point-of-Care Application: Recent Evaluations and Future Needs?

    OpenAIRE

    Blacksell, Stuart D

    2012-01-01

    Dengue fever, dengue haemorrhagic fever, and dengue shock syndrome (DF/DHF/DSS) are tropical diseases that cause significant humanitarian and economic hardship. It is estimated that more than 2.5 billion people are at risk of infection and more than 100 countries have endemic dengue virus transmission. Laboratory tests are essential to provide an accurate diagnosis of dengue virus infection so that appropriate treatment and patient management may be administered. In many dengue endemic settin...

  12. Dengue virus-specific cross-reactive CD8+ human cytotoxic T lymphocytes.

    OpenAIRE

    Bukowski, J F; Kurane, I; Lai, C J; Bray, M; Falgout, B; Ennis, F A

    1989-01-01

    Stimulation with live dengue virus of peripheral blood mononuclear cells from a dengue virus type 4-immune donor generated virus-specific, serotype-cross-reactive, CD8+, class I-restricted cytotoxic T lymphocytes (CTL) capable of lysing dengue virus-infected cells and cells pulsed with dengue virus antigens of all four serotypes. These CTL lysed autologous fibroblasts infected with vaccinia virus-dengue virus recombinant viruses containing the E gene or several nonstructural dengue virus type...

  13. Evaluation of Nonstructural 1 Antigen Assays for the Diagnosis and Surveillance of Dengue in Singapore

    OpenAIRE

    Pok, Kwoon-Yong; Lai, Yee-Ling; Sng, Joshua; Ng, Lee-Ching

    2010-01-01

    Early and accurate diagnosis of dengue is imperative for disease surveillance, which helps in the control of dengue in endemic countries. In this study, we evaluated the performance of three commercially available dengue nonstructural 1 (NS1) antigen assays (Bio-Rad Platelia™ Dengue NS1 Antigen ELISA, PanBio Dengue Early ELISA, and Bio-Rad Dengue NS1 Antigen Strip test) and compared them with reverse-transcription polymerase chain reaction (RT-PCR) and other commercially available serological...

  14. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

    OpenAIRE

    Idrees, Sobia; Ashfaq, Usman A

    2012-01-01

    Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to e...

  15. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    OpenAIRE

    Natthanej Luplertlop

    2014-01-01

    Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of ...

  16. Internal travel and risk of dengue transmission in Colombia.

    Science.gov (United States)

    Chaparro, Pablo E; de la Hoz, Fernando; Lozano Becerra, Juan C; Repetto, Silvia A; Alba Soto, Catalina D

    2014-09-01

    Human behavior plays a key role in the dynamics of dengue transmission. However, research on the relationship between human movement and dengue transmission within endemic countries is limited. From January 2008 to December 2011, the authors of this study conducted a retrospective analysis of imported dengue infections in Bogotá, Colombia. Bogotá is a vector-transmission-free city that is also the capital district and most populated municipality in Colombia. The study revealed that 1) Bogotá inhabitants acquired dengue infection in diverse localities throughout the country but the largest proportion of cases (35.6%) were contracted at popular tourist destinations in dengue-endemic areas near Bogotá (<200-km radius from city limits), and 2) the number of imported dengue cases increased after major holidays, a transmission pattern not seen in dengue-endemic areas, where disease incidence correlates with rainy periods. It is therefore recommended that physicians consider the effect of travel when diagnosing their patients' illnesses, especially outside dengue-endemic areas where diagnosis of the disease can be challenging due to its nonspecific symptoms. The study also showed that analysis of dengue cases imported to regions free of vector transmission can generate an evidence-based model for characterizing the impact of human movement on the spread of diseases like dengue in countries where they are endemic. PMID:25418771

  17. Knowledge and prevention measures against dengue in southern Nepal

    Directory of Open Access Journals (Sweden)

    Biswas Neupane

    2014-12-01

    Full Text Available Objective: To ascertain the knowledge and prevention measures against dengue among selected adult population in southern Nepal. Methods: A cross sectional study was conducted in Rapti Zonal Hospital, Dang and Bharatpur Hospital, Chitwan during August-November, 2011. A total of 212 patients were interviewed regarding their knowledge and practices about dengue fever. Serum samples were collected and investigated for the presence of anti-dengue IgM antibodies by IgM-ELISA. Results: Data from 156 patients greater than 15 years were analyzed. Among them, 21 samples were found to possess anti-dengue IgM antibodies by ELISA. Females, economically active people, farmers, unemployed and housewives were more frequently affected by dengue. Of the total, 118 (76% were reported to know the disease dengue. Fever, headache and myalgia were the most known symptoms and house drains and kitchen garden were known as the most common breeding sites of mosquitoes. Garbage disposal, use of mosquito nets and covering water containers were the best known preventive measures. Conclusions: The overall knowledge of dengue was high, but females, old persons, unemployed and housewives had relatively little knowledge of dengue. Therefore, these groups may need special attention in future dengue education programs. Persons with knowledge of the disease more frequently reported the use of preventive measures, indicating the value of education programs as a tool in dengue prevention.

  18. The prevention and control of dengue after Typhoon Haiyan

    Directory of Open Access Journals (Sweden)

    Charito Aumentado

    2015-11-01

    Full Text Available Objective: Many of the areas in the Philippines affected by Typhoon Haiyan are endemic for dengue; therefore, dengue prevention was a priority in the initial post-disaster risk assessment. We describe the dengue prevention and response strategies applied after Haiyan. Methods: The dengue response was implemented by a wide range of national and international stakeholders. Priorities included the rapid re-establishment of an effective surveillance system to quickly identify new dengue cases, monitor trends and determine the geographical distribution of cases. Dengue rapid diagnostic tests (RDTs were distributed to sentinel health facilities, and comprehensive vector control activities and entomological surveys were implemented. Several training sessions for key stakeholders and awareness campaigns for communities were organized. Results: There were RDT-positive dengue cases reported from urban and semi-urban areas where entomological surveys also confirmed a high density of Aedes aegypti mosquitoes. Although there was an increase in dengue cases in January 2014, the number of cases remained below the epidemic threshold throughout the remaining months of 2014. Discussion: There was no large outbreak of dengue after Typhoon Haiyan, possibly due to the targeted, multifaceted and rapid response for dengue after Haiyan. However, surveillance differed after Haiyan, making comparisons with previous years difficult. Multiple players contributed to the response that was also facilitated by close communication and coordination within the Health Cluster.

  19. Postmortem Diagnosis of Dengue as an Epidemiological Surveillance Tool.

    Science.gov (United States)

    Cavalcanti, Luciano Pamplona de Góes; Braga, Deborah Nunes de Melo; da Silva, Lívia Maria Alexandre; Aguiar, Marina Gondim; Castiglioni, Mariana; Silva-Junior, José Udevanier; Araújo, Fernanda Montenegro de Carvalho; Pereira, Renata Allana da Costa; Malta, Danielle Lima; Pompeu, Margarida Maria de Lima

    2016-01-01

    Dengue remains a problem in Brazil, and a substantial number of cases that progress to death are not diagnosed by health services. We evaluated the impact of a protocol adopted by the Coroner's Office Rocha Furtado (CO-RF) for the detection of unreported deaths from dengue in Brazil. We evaluated prospectively cases of deaths referred to the CO-RF with suspicion of dengue and those referred with other diagnosis in which the pathologists suspected dengue as the cause of death. Biological material was collected from all bodies autopsied, for which the suspected cause of death was dengue, between January 2011 and December 2012. Of the 214 bodies autopsied, 134 (62.6%) tested positive for dengue; of these cases, 121 were classified as dengue according to the World Health Organization's case definition (1997 or 2009, as appropriate). Thus, CO-RF detected 90 deaths from dengue, which were not suspected during disease progression. This CO-RF protocol, through a combined effort of the surveillance and laboratory teams, increased the detection of fatal dengue cases by 5-fold. This is the largest series of autopsies performed in cases of death related to dengue in the world to date.

  20. Imported cases of dengue in Poland and their diagnosis.

    Science.gov (United States)

    Pancer, Katarzyna; Szkoda, Marek Tomasz; Gut, Włodzimierz

    2014-01-01

    Infections with dengue virus are transmitted by mosquitoes. In tropical areas, it is mainly spread by Aedes aegypti while in countries with lower temperatures by Aedes albopictus. Since 2010, autochthonous cases of dengue are also reported in Europe. There are 4 serotypes of dengue virus (DENV). No correlation between clinical presentation of disease and virus type, however, were determined. Nevertheless, reinfection with different type of DENV may lead to a serious, life-threatening condition. An estimated 100 million persons are infected with dengue virus per year. Of them, approximately a half (mainly children) develop the symptoms of dengue fever (DF), dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Fatality is high in case of severe dengue. Dengue is a serious condition provided there is a presence of IgG antibodies directed against antigens of particular DENV serotypes, associated with primary infection caused by different serotype or transferred from infected mother to her child. For adequate dengue laboratory diagnosis, it is required to apply a set of various diagnostic methods. Within the family Flaviviridae, cross-reactivity is reported, which may lead to the occurrence of false-positive results. In Poland, differential diagnosis with different Flavivirus species is of special importance as it is an endemic area for tick-borne encephalitis (TBE). Thus, data regarding history of patient's immunization against TBE or yellow fever should be also taken into consideration as important in interpretation of results of serological examination. PMID:25848785

  1. Cost of Dengue Vector Control Activities in Malaysia.

    Science.gov (United States)

    Packierisamy, P Raviwharmman; Ng, Chiu-Wan; Dahlui, Maznah; Inbaraj, Jonathan; Balan, Venugopalan K; Halasa, Yara A; Shepard, Donald S

    2015-11-01

    Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently spread rapidly, especially in the tropical countries of the Americas and Asia-Pacific regions. It is endemic in Malaysia, with an annual average of 37,937 reported dengue cases from 2007 to 2012. This study measured the overall economic impact of dengue in Malaysia, and estimated the costs of dengue prevention. In 2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its National Dengue Vector Control Program. This spending represented US$1,591 per reported dengue case and US$2.68 per capita population. Most (92.2%) of this spending occurred in districts, primarily for fogging. A previous paper estimated the annual cost of dengue illness in the country at US$102.2 million. Thus, the inclusion of preventive activities increases the substantial estimated cost of dengue to US$175.7 million, or 72% above illness costs alone. If innovative technologies for dengue vector control prove efficacious, and a dengue vaccine was introduced, substantial existing spending could be rechanneled to fund them. PMID:26416116

  2. An innovative forecasting and dashboard system for Malaysian dengue trends

    Science.gov (United States)

    Jamil, Jastini Mohd; Shaharanee, Izwan Nizal Mohd

    2016-08-01

    Dengue fever has been recognized in over 100 countries and 2.5 billion people live in areas where dengue is endemic. It is currently a serious arthropod-borne disease, affecting around 50-100 million people worldwide every year. Dengue fever is also prevalent in Malaysia with numerous cases including mortality recorded over the past year. In 2012, a total of 21,900 cases of dengue fever were reported with 35 deaths. Dengue, a mosquito-transmitted virus, causes a high fever accompanied by significant pain in afflicted patient and the Aedes Aegypti mosquito is the primary disease carrier. Knowing the dangerous effect of dengue fever, thus one of the solutions is to implement an innovative forecasting and dashboard system of dengue spread in Malaysia, with emphasize on an early prediction of dengue outbreak. Specifically, the model developed will provide with a valuable insight into strategically managing and controlling the future dengue epidemic. Importantly, this research will deliver the message to health policy makers such as The Ministry of Health Malaysia (MOH), practitioners, and researchers of the importance to integrate their collaboration in exploring the potential strategies in order to reduce the future burden of the increase in dengue transmission cases in Malaysia.

  3. Knowledge and prevention measures against dengue in southern Nepal

    Institute of Scientific and Technical Information of China (English)

    Biswas Neupane; Komal Raj Rijal; Megha Raj Banjara; Basu Dev Pandey

    2014-01-01

    Objective: To ascertain the knowledge and prevention measures against dengue among selected adult population in southern Nepal. Methods: A cross sectional study was conducted in Rapti Zonal Hospital, Dang and Bharatpur Hospital, Chitwan during August-November, 2011. A total of 212 patients were interviewed regarding their knowledge and practices about dengue fever. Serum samples were collected and investigated for the presence of anti-dengue IgM antibodies by IgM-ELISA. Results: Data from 156 patients greater than 15 years were analyzed. Among them, 21 samples were found to possess anti-dengue IgM antibodies by ELISA. Females, economically active people, farmers, unemployed and housewives were more frequently affected by dengue. Of the total, 118 (76%) were reported to know the disease dengue. Fever, headache and myalgia were the most known symptoms and house drains and kitchen garden were known as the most common breeding sites of mosquitoes. Garbage disposal, use of mosquito nets and covering water containers were the best known preventive measures.Conclusions:The overall knowledge of dengue was high, but females, old persons, unemployed and housewives had relatively little knowledge of dengue. Therefore, these groups may need special attention in future dengue education programs. Persons with knowledge of the disease more frequently reported the use of preventive measures, indicating the value of education programs as a tool in dengue prevention.

  4. All Serotypes of Dengue Viruses Circulating in Kuala Lumpur, Malaysia

    Directory of Open Access Journals (Sweden)

    M.H. Chew

    2012-03-01

    Full Text Available Dengue is a severe disease caused by dengue virus (DENV, transmitted to human being by infected Aedes mosquitoes. It is a major public health concern in Southeast Asia due to its fatality in the form of hemorrhagic fever (DHF and dengue shock syndrome (DSS. The objective of the study was to isolate and identify dengue virus serotypes prevalent in endemic areas of Kuala Lumpur and Selangor in Malaysia by virus culture, indirect immunoflurecent assay and molecular techniques. A total number of 232 sera samples were obtained from patients with clinical manifestations of dengue fever reported to University Kebangsaan Malaysia Medical Centre (UKMMC. The sera samples collected, were analyzed for IgM/IgG detection for the assessment of primary and secondary dengue fever, propagation in cell-line C36/36, Indirect Immunoflurecent Assay (IFA and RT-PCR. The study confirmed 46 dengue cases where 15 (32.61% were dual infections with DENV-1 and DENV- 4, 12 (26.09% dual infections with DENV-3 and DENV-4, and 11 (23.91% were dual infection with DENV-2 and DENV-4. Only 1 (2.17% was dengue infection with DENV-3 and 7 (15.22% were with DENV-4. Dengue serotype 4 was the most common serotype identified in the present study .The highest number of dengue cases detected in Cheras, Kuala Lumpur where all 4 types of dengue virus were prevalent. All serotypes of dengue viruses circulation only in Kuala Lumpur and Selangor Malaysia, needs further strengthening of the dengue preventive measure in the city areas and in the country.

  5. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

    Science.gov (United States)

    Conway, Michael J.; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M.; Klimstra, William B.; Fikrig, Erol; Colpitts, Tonya M.

    2016-01-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1–4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  6. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    Science.gov (United States)

    Conway, Michael J; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M; Klimstra, William B; Fikrig, Erol; Colpitts, Tonya M

    2016-09-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  7. SPECTRUM OF HEPATIC DYSFUNCTION IN DENGUE FEVER

    Directory of Open Access Journals (Sweden)

    Balaraj

    2014-03-01

    Full Text Available INTRODUCTION: Dengue infection is a common and major health problem across the globe and more so in India with its varied presentations and atypical parameters on investigations makes us to have more knowledge of these. MATERIALS AND METHODS: A total of 60 patients admitted to KIMS hospital and research centre, Bangalore with the confirmed diagnosis of dengue fever in 2013 were studied. RESULTS: An analysis of 60 confirmed cases of dengue showed that 70% had hepatic dysfunction in form of raised SGOT [>2ULN], 60% had SGPT [>2ULN], 3 had jaundice. All patients had fever; many patients had pain abdomen and vomiting as predominant complaint apart from myalgia. DISCUSSION: In our study mild to moderate hepatic dysfunction in the form of elevated enzymes were seen in most of the patients in consistent with other studies. Hepatic dysfunction was seen more in Patients with severe dengue infections similar to other studies. CONCLUSION: Thus it is necessary to have knowledge of this entity and diagnose early and start treatment to prevent the complications

  8. [Dengue vaccines. A reality for Argentina?].

    Science.gov (United States)

    Orellano, Pablo W; Salomón, Oscar D

    2016-01-01

    Dengue outbreaks have occurred yearly in Argentina since 1998. A number of candidate vaccines have been tested in endemic countries. The most advanced one was licensed in three countries of Latin America for children over 9 years of age. In the present article the benefits and drawbacks of these vaccines as well as the challenges for the implementation of a vaccination strategy in Argentina are discussed. Furthermore, a risk stratification strategy with new criteria and a multidisciplinary vision is suggested as a possible path for the assessment of the pertinence of a vaccination program in areas showing the highest risk of dengue transmission and/or for people at the greatest risk of developing severe dengue. It is also suggested that the definition regarding the status of endemicity should take into account the local realities. Finally, this paper proposes a broad discussion on the evidences, the expected impact and instrumental aspects that would be involved in the incorporation of a dengue vaccine, marketed or in development, into the national immunization program, and especially which subpopulation should be targeted for the immunization strategy to be cost-effective.

  9. Vaccination Against Dengue: Challenges and Current Developments.

    Science.gov (United States)

    Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

    2016-01-01

    Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

  10. Dengue Virus Genome Uncoating Requires Ubiquitination

    Directory of Open Access Journals (Sweden)

    Laura A. Byk

    2016-06-01

    Full Text Available The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process.

  11. [Dengue vaccines. A reality for Argentina?].

    Science.gov (United States)

    Orellano, Pablo W; Salomón, Oscar D

    2016-01-01

    Dengue outbreaks have occurred yearly in Argentina since 1998. A number of candidate vaccines have been tested in endemic countries. The most advanced one was licensed in three countries of Latin America for children over 9 years of age. In the present article the benefits and drawbacks of these vaccines as well as the challenges for the implementation of a vaccination strategy in Argentina are discussed. Furthermore, a risk stratification strategy with new criteria and a multidisciplinary vision is suggested as a possible path for the assessment of the pertinence of a vaccination program in areas showing the highest risk of dengue transmission and/or for people at the greatest risk of developing severe dengue. It is also suggested that the definition regarding the status of endemicity should take into account the local realities. Finally, this paper proposes a broad discussion on the evidences, the expected impact and instrumental aspects that would be involved in the incorporation of a dengue vaccine, marketed or in development, into the national immunization program, and especially which subpopulation should be targeted for the immunization strategy to be cost-effective. PMID:27028058

  12. Dengue Virus Genome Uncoating Requires Ubiquitination

    Science.gov (United States)

    Byk, Laura A.; Iglesias, Néstor G.; De Maio, Federico A.; Gebhard, Leopoldo G.; Rossi, Mario

    2016-01-01

    ABSTRACT The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. PMID:27353759

  13. Dengue platelets meet Sir Arthur Conan Doyle.

    Science.gov (United States)

    Bray, Paul F

    2013-11-14

    In this issue of Blood, Hottz et al provide compelling evidence that dengue virus (DV) induces (1) platelet synthesis of interleukin-1b (IL-1b); (2) platelet-derived IL-1b–containing microvesicles (MVs) that increase vascular permeability; and (3) DV-triggered inflammasome activation in platelets.

  14. Dengue Fever in the United States

    Centers for Disease Control (CDC) Podcasts

    2012-04-09

    Dr. Amesh Adalja, an associate at the Center for Biosecurity and clinical assistant professor at the University of Pittsburgh School, of Medicine, discusses dengue fever outbreaks in the United States.  Created: 4/9/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/16/2012.

  15. Visualizing dengue virus through Alexa Fluor labeling.

    Science.gov (United States)

    Zhang, Summer; Tan, Hwee Cheng; Ooi, Eng Eong

    2011-01-01

    The early events in the interaction between virus and cell can have profound influence on the outcome of infection. Determining the factors that influence this interaction could lead to improved understanding of disease pathogenesis and thus influence vaccine or therapeutic design. Hence, the development of methods to probe this interaction would be useful. Recent advancements in fluorophores development and imaging technology can be exploited to improve our current knowledge on dengue pathogenesis and thus pave the way to reduce the millions of dengue infections occurring annually. The enveloped dengue virus has an external scaffold consisting of 90 envelope glycoprotein (E) dimers protecting the nucleocapsid shell, which contains a single positive strand RNA genome. The identical protein subunits on the virus surface can thus be labeled with an amine reactive dye and visualized through immunofluorescent microscopy. Here, we present a simple method of labeling of dengue virus with Alexa Fluor succinimidyl ester dye dissolved directly in a sodium bicarbonate buffer that yielded highly viable virus after labeling. There is no standardized procedure for the labeling of live virus and existing manufacturer's protocol for protein labeling usually requires the reconstitution of dye in dimethyl sulfoxide. The presence of dimethyl sulfoxide, even in minute quantities, can block productive infection of virus and also induce cell cytotoxicity. The exclusion of the use of dimethyl sulfoxide in this protocol thus reduced this possibility. Alexa Fluor dyes have superior photostability and are less pH-sensitive than the common dyes, such as fluorescein and rhodamine, making them ideal for studies on cellular uptake and endosomal transport of the virus. The conjugation of Alexa Fluor dye did not affect the recognition of labeled dengue virus by virus-specific antibody and its putative receptors in host cells. This method could have useful applications in virological studies.

  16. Dengue virus targets the adaptor protein MITA to subvert host innate immunity.

    Science.gov (United States)

    Yu, Chia-Yi; Chang, Tsung-Hsien; Liang, Jian-Jong; Chiang, Ruei-Lin; Lee, Yi-Ling; Liao, Ching-Len; Lin, Yi-Ling

    2012-01-01

    Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN). We found that activation of interferon regulatory factor 3 (IRF3) triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a protease-dependent mechanism. The key adaptor protein in type I interferon pathway, human mediator of IRF3 activation (MITA) but not the murine homologue MPYS, was cleaved in cells infected with DEN-1 or DEN-2 and with expression of the enzymatically active protease NS2B3. The cleavage site of MITA was mapped to LRR↓(96)G and the function of MITA was suppressed by dengue protease. DEN replication was reduced with overexpression of MPYS but not with MITA, while DEN replication was enhanced by MPYS knockdown, indicating an antiviral role of MITA/MPYS against DEN infection. The involvement of MITA in DEN-triggered innate immune response was evidenced by reduction of IRF3 activation and IFN induction in cells with MITA knockdown upon DEN-2 infection. NS2B3 physically interacted with MITA, and the interaction and cleavage of MITA could be further enhanced by poly(dA:dT) stimulation. Thus, we identified MITA as a novel host target of DEN protease and provide the molecular mechanism of how DEN subverts the host innate immunity.

  17. Dengue virus targets the adaptor protein MITA to subvert host innate immunity.

    Directory of Open Access Journals (Sweden)

    Chia-Yi Yu

    Full Text Available Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN. We found that activation of interferon regulatory factor 3 (IRF3 triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a protease-dependent mechanism. The key adaptor protein in type I interferon pathway, human mediator of IRF3 activation (MITA but not the murine homologue MPYS, was cleaved in cells infected with DEN-1 or DEN-2 and with expression of the enzymatically active protease NS2B3. The cleavage site of MITA was mapped to LRR↓(96G and the function of MITA was suppressed by dengue protease. DEN replication was reduced with overexpression of MPYS but not with MITA, while DEN replication was enhanced by MPYS knockdown, indicating an antiviral role of MITA/MPYS against DEN infection. The involvement of MITA in DEN-triggered innate immune response was evidenced by reduction of IRF3 activation and IFN induction in cells with MITA knockdown upon DEN-2 infection. NS2B3 physically interacted with MITA, and the interaction and cleavage of MITA could be further enhanced by poly(dA:dT stimulation. Thus, we identified MITA as a novel host target of DEN protease and provide the molecular mechanism of how DEN subverts the host innate immunity.

  18. The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection.

    Science.gov (United States)

    Hu, Hui-Mei; Chen, Hsin-Wei; Hsiao, Yu-Ju; Wu, Szu-Hsien; Chung, Han-Hsuan; Hsieh, Chun-Hsiang; Chong, Pele; Leng, Chih-Hsiang; Pan, Chien-Hsiung

    2016-07-01

    Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine. PMID:26901482

  19. A Tetravalent Dengue Vaccine Based on a Complex Adenovirus Vector Provides Significant Protection in Rhesus Monkeys against All Four Serotypes of Dengue Virus▿

    OpenAIRE

    Raviprakash, Kanakatte; Wang, Danher; Ewing, Dan; Holman, David H.; Block, Karla; Woraratanadharm, Jan; Chen, Lan; Hayes, Curtis; Dong., John Y.; Porter, Kevin

    2008-01-01

    Nearly a third of the human population is at risk of infection with the four serotypes of dengue viruses, and it is estimated that more than 100 million infections occur each year. A licensed vaccine for dengue viruses has become a global health priority. A major challenge to developing a dengue vaccine is the necessity to produce fairly uniform protective immune responses to all four dengue virus serotypes. We have developed two bivalent dengue virus vaccines, using a complex adenovirus vect...

  20. The burden of dengue: Jundiaí, Brazil - January 2010

    Directory of Open Access Journals (Sweden)

    Christian Julián Villabona Arenas

    2012-08-01

    Full Text Available OBJECTIVE: To study the antibody prevalence against dengue in the municipality of Jundiaí, São Paulo, Brazil, due to the low number of official confirmed autochthonous cases. METHODS: A serological study on dengue infection was conducted during January 2010 and previous reports on dengue and entomological surveillance during that period were reviewed. RESULTS: A prevalence of 7.8% IgG positive (68:876 was found. Furthermore, based on the detection of IgM antibodies in five samples, it was observed that the incidence of dengue in the city at the time of the survey contrasts with the absence of notifications by local health authorities over the same period of time. CONCLUSION: These results highlight the discrepancies between the actual and the detected number of dengue infections, possibly due to significant numbers of asymptomatic infections aggravated by difficulties with dengue clinical diagnosis.